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Molecules Mediating Allergic and Autoimmune Inflammation: Commemorative Issue in Honor of Professor Christopher W. K. Lam’s Research Achievements on the Occasion of His 70th Birthday

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 November 2016) | Viewed by 106592

Special Issue Editor

Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China
Interests: mast cell; allergic rhinitis; cytokines; signal transduction molecules; inflammation; eosinophils; allergic asthma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammation is part of the complex surveillance response of our body to disturbances of homeostasis, such as exposure to pathogens or irritants, cell injury, or tissue damage. It is orchestrated by effector molecules (cytokines, chemokines, and adhesion molecules) mediating intercellular communication among immune cells (macrophages, natural killer cells, T-helper lymphocytes, B lymphocytes, mast cells, basophils, and eosinophils) and participating tissues (blood vessels, skin, lungs, heart, and kidneys). Inflammation is a double-edged sword. Whilst short-term, acute-phase inflammation can always accelerate restoration of homeostasis, long-term on-going inflammation may cause chronic degenerative diseases such as allergy, autoimmunity, diabetes and renal failure. Not infrequently, exaggerated (inappropriately severe) or uncontrolled (unnecessarily lengthy) inflammation is caused by dysregulation of molecules mediating inflammation. Allergic and autoimmune diseases are known to have resulted from derangements of these intercellular messengers. Development of therapeutic strategies for correction of such messenger pathology should be helpful in clinical management of diseases of cellular miscommunication.

Our journal is pleased to be publishing a commemorative issue in honor of Professor Christopher W. K. Lam for his outstanding research contributions on “Molecules Mediating Allergic and Autoimmune Inflammation”.

Professor Lam is at present employed at the Macau University of Science and Technology, Macau, China as (1) Chair Professor and Vice Dean of the Faculty of Health Sciences, (2) Director of Laboratory Medicine at the University Hospital, and (3) Principal Researcher in the State Key Laboratory of Quality Research in Chinese Medicine. He took up these appointments in 2010 upon retiring from The Chinese University of Hong Kong and Prince of Wales Hospital, Hong Kong, China as (1) Professor, Chairman and Chief of Service of the Department of Chemical Pathology, (2) Director of Clinical Immunology Unit, and (3) Assistant Dean of Medicine (Research).

The above academic and professional responsibilities have facilitated Professor Lam’s active research in clinical and experimental medicine since the 1990s covering allergy and clinical immunology, nephrology, lipidology, endocrinology, toxicology, and clinical trials of Chinese medicines. He has to-date published >550 scientific papers with a total citation number >12,500 and h-score of 55. Among them, studies of allergy (allergic rhinitis, asthma and atopic dermatitis) and autoimmune diseases (systemic lupus erythematosus (SLE) and rheumatoid arthritis) contributed >140 papers. Partly because of his work on the immunopathology of severe acute respiratory syndrome (SARS), Professor Lam was conferred an inaugural Distinguished Award in Laboratory Medicine and Patient Care by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) in 2008. In this same year, his paper (of which I was the first author) on Th17-mediated inflammation in SLE was subsequently commended as one of the five top-cited publications in Clincial Immunology from 2006–2010.

In honor of Professor Lam’s outstanding career achievements on the occasion of his 70th birthday in 2016, this commemorative issue of Molecules welcomes submission of previously unpublished manuscripts from original work or reviews on “Molecules Mediating Allergic and Autoimmune Inflammation”. We plan to receive submissions from 1 February to 30 November 2016 and manuscripts will be published online on an ongoing basis after being processed.

Prof. Dr. Chun Kwok Wong
Guest Editor
5 January 2016

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cytokines
  • chemokines
  • adhesion molecules
  • T-helper lymphocyte pathways
  • intracellular signaling
  • allergic rhinitis
  • asthma
  • atopic dermatitis
  • systemic lupus erythematosus
  • rheumatoid arthritis
  • Chinese herbal medicine

Published Papers (12 papers)

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Research

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6332 KiB  
Article
The Transcriptome of Type I Murine Astrocytes under Interferon-Gamma Exposure and Remyelination Stimulus
by Anna Kudriaeva, Vladimir V. Galatenko, Diana V. Maltseva, Nadezhda A. Khaustova, Ekaterina Kuzina, Alexander G. Tonevitsky, Alexander Gabibov and Alexey Belogurov
Molecules 2017, 22(5), 808; https://doi.org/10.3390/molecules22050808 - 15 May 2017
Cited by 18 | Viewed by 5599
Abstract
Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood–brain barrier—in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report [...] Read more.
Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood–brain barrier—in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report here the transcriptomal profiling of astrocytes treated using IFNγ and benztropine, a putative remyelinization agent. Our findings indicate that the expression of genes involved in antigen processing and presentation in astrocytes are significantly upregulated upon IFNγ exposure, emphasizing the critical role of this cytokine in the redirection of immune response towards self-antigens. Data reported herein support previous observations that the IFNγ-induced JAK-STAT signaling pathway may be regarded as a valuable target for pharmaceutical interventions. Full article
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435 KiB  
Article
Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers
by Kam Lun Hon, Kathy Yin Ching Tsang, Jeng Sum C. Kung, Ting Fan Leung, Christopher W. K. Lam and Chun Kwok Wong
Molecules 2017, 22(2), 291; https://doi.org/10.3390/molecules22020291 - 14 Feb 2017
Cited by 20 | Viewed by 13946
Abstract
Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), [...] Read more.
Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), selected seromarkers of T regulatory (Treg), T helper (Th) and antigen-presenting cells (APC) are associated with clinical signs of disease severity and quality of life. Disease severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index, and quality of life with the Children’s Dermatology Life Quality Index (CDLQI) in AD patients ≤18 years old. Concentrations of anti-staphylococcus enterotoxin A and B immunoglobulin E (anti-SEA and anti-SEB), selected Treg/Th/APC chemokines, skin hydration and transepidermal water loss (TEWL) were measured in these patients. Forty patients with AD [median (interquartile range) age of 13.1 (7.9) years) were recruited. Backward stepwise linear regression (controlling for age, personal allergic rhinitis and asthma, and other blood markers) showed the serum anti-SEB level was positively associated with S. aureus and S. epidermidis isolations, objective SCORAD, clinical signs and CDLQI. TNF-α (a Th1 cytokine) was positively associated with objective SCORAD (B = 4.935, p = 0.010), TGF-β (a Treg cytokine) negatively with disease extent (B = −0.015, p = 0.001), IL-18 (an APC cytokine) positively with disease extent (B = 0.438, p = 0.001) and with TEWL (B = 0.040, p = 0.010), and IL-23 (an APC cytokine) negatively with disease extent (B = −2.812, p = 0.006) and positively with pruritus (B = 0.387, p = 0.007). Conclusions: Blood levels of anti-SEB, Th1, Treg and APC cytokines are correlated with various clinical signs of AD. AD is a systemic immunologic disease involving Staphylococcus aureus, cellular, humoral, cytokine and chemokine pathophysiology. Full article
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Article
Capparis spinosa Fruit Ethanol Extracts Exert Different Effects on the Maturation of Dendritic Cells
by Azeguli Hamuti, Jinyu Li, Fangfang Zhou, Adila Aipire, Ji Ma, Jianhua Yang and Jinyao Li
Molecules 2017, 22(1), 97; https://doi.org/10.3390/molecules22010097 - 07 Jan 2017
Cited by 17 | Viewed by 7289
Abstract
Capparis spinosa L. (C. spinosa) has been used as food and traditional medicine and shows anti-inflammatory and anti-oxidant activities. Here, we prepared the C. spinosa fruit ethanol extracts (CSEs) using different procedures and investigated the effects of CSE on the maturation [...] Read more.
Capparis spinosa L. (C. spinosa) has been used as food and traditional medicine and shows anti-inflammatory and anti-oxidant activities. Here, we prepared the C. spinosa fruit ethanol extracts (CSEs) using different procedures and investigated the effects of CSE on the maturation of mouse bone marrow-derived dendritic cells (DCs) in the absence or presence of lipopolysaccharide (LPS). DC maturation and cytokine production were detected by flow cytometry and ELISA, respectively. We obtained three different CSEs and dissolved in water or DMSO, named CSE2W, CSEMW, CSE3W, CSE2D, CSEMD, and CSE3D, respectively. These CSEs showed different effects on DC maturation. CSEMW and CSEMD significantly increased the expressions of CD40, CD80, and CD86, in a dose-dependent manner. CSE2W and CSE2D also showed a modest effect on DC maturation, which enhanced the expression of CD40. CSE3W and CSE3D did not change DC maturation but suppressed LPS-induced DC maturation characterized by the decreased levels of CD40 and CD80. CSE3W and CSE3D also significantly inhibited the secretions of IL-12p40, IL-6, IL-1β, and TNF-α induced by LPS. CSE3W further increased the level of IL-10 induced by LPS. Moreover, CSE3D suppressed LPS-induced DC maturation in vivo, which decreased the expressions of CD40 and CD80. These results suggested that CSE3W and CSE3D might be used to treat inflammatory diseases. Full article
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Article
Serum Interleukin-34 Levels Are Elevated in Patients with Systemic Lupus Erythematosus
by Hongxu Wang, Ju Cao and Xiaofei Lai
Molecules 2017, 22(1), 35; https://doi.org/10.3390/molecules22010035 - 28 Dec 2016
Cited by 34 | Viewed by 5857
Abstract
Interleukin-34 (IL-34) was initially identified as an alternative ligand for the colony-stimulating factor-1 receptor (CSF-1R) to mediate the biology of mononuclear phagocytic cells. Recently, IL-34 was found to be associated with chronic inflammation, such as in rheumatoid arthritis (RA). Both RA and systemic [...] Read more.
Interleukin-34 (IL-34) was initially identified as an alternative ligand for the colony-stimulating factor-1 receptor (CSF-1R) to mediate the biology of mononuclear phagocytic cells. Recently, IL-34 was found to be associated with chronic inflammation, such as in rheumatoid arthritis (RA). Both RA and systemic lupus erythematosus (SLE) are multifactorial autoimmune diseases and are characterized by excessive immune and inflammatory responses. Thus, we investigated whether IL-34 is involved in the pathogenesis of SLE. In all, 78 SLE patients and 53 healthy controls were enrolled in the research. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the concentrations of serological IL-34. Then serum IL-34 levels between the SLE group and healthy controls were analyzed by the Mann-Whitney U test. Meanwhile, the correlations between the serum IL-34 levels and disease activity indexes and other established serum markers were assessed. Furthermore, the serum IL-34 levels of 20 active SLE patients were reevaluated when diseases were in the remission stage from corticosteroids or immunosuppressive drugs. Serum IL-34 levels were significantly higher in SLE patients compared to healthy controls. Their levels were remarkably associated with accumulation of the clinical features of SLE. Additionally, IL-34 titers were positively correlated with the SLE disease activity indexes, anti-double-stranded DNA antibody (anti-dsDNA) titers and C-reactive protein (CRP) levels, and inversely with complement3 (C3) levels. Moreover, serum IL-34 levels were significantly decreased after successful treatment of SLE. Serum IL-34 could be a candidate biomarker for SLE as there are elevated serum levels in treatment-naive SLE patients and we saw a significant decrease after effective treatment. Full article
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1166 KiB  
Article
Circulating IL-27 Is Elevated in Rheumatoid Arthritis Patients
by Xiaofei Lai, Hongxu Wang, Ju Cao, Ying Li, Yubing Dai, Yu Xiang and Liping Zhang
Molecules 2016, 21(11), 1565; https://doi.org/10.3390/molecules21111565 - 18 Nov 2016
Cited by 32 | Viewed by 5053
Abstract
Cytokines are key immunoregulatory molecules that regulate T lymphocyte-mediated immune responses and inflammatory reactions. We determined whether there is aberrant expression of interleukin-27 (IL-27) in rheumatoid arthritis (RA) patients and investigated the clinical significance of these changes. IL-27 is a key cellular factor [...] Read more.
Cytokines are key immunoregulatory molecules that regulate T lymphocyte-mediated immune responses and inflammatory reactions. We determined whether there is aberrant expression of interleukin-27 (IL-27) in rheumatoid arthritis (RA) patients and investigated the clinical significance of these changes. IL-27 is a key cellular factor that regulates the differentiation of CD4+ T cells, which can secrete interleukin-10 (IL-10) and interleukin-17 (IL-17) in vivo. Concentrations of serum IL-27 in 67 RA patients, and 36 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay (ELISA). Results showed that concentrations of serum IL-27 in all RA patients were significantly higher than in healthy control subjects, and there was a significant and positive correlation between serum IL-27 levels and disease activity in all RA patients. Levels of serum IL-27 in RA patients were significantly correlated with disease activity score in 28 joints (DAS28). Moreover, immunosuppressive treatment with leflunomide downregulated the levels of IL-27 in active RA patients. Therefore, the elevated production of circulating T cell inflammatory factors contributes to the pathogenesis of RA, and serum IL-27 could potentially serve as a new biomarker of RA disease activity. Full article
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Article
Aberrant Expression of Novel Cytokine IL-38 and Regulatory T Lymphocytes in Childhood Asthma
by Man Chu, Ida M.T. Chu, Edmund C.M. Yung, Christopher W.K. Lam, Ting F. Leung, Gary W.K. Wong and Chun K. Wong
Molecules 2016, 21(7), 933; https://doi.org/10.3390/molecules21070933 - 18 Jul 2016
Cited by 49 | Viewed by 6108
Abstract
We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4+CD25+CD134+ T lymphocytes as well as CD4+CD25high [...] Read more.
We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4+CD25+CD134+ T lymphocytes as well as CD4+CD25highFoxP3+ and CD4+CD25highCD127 Treg lymphocytes from 40 asthmatic patients and 20 normal control (NC) subjects were studied using ELISA, qPCR and flow cytometry. Serum and supernatant cytokines/chemokines were determined by multiplex assay. Serum IL-38, IL-5, IL-17, IL-6, interferon-γ, periostin, IL-1β and IL-13 concentrations were significantly higher in asthmatic patients with or without steroid treatment than those in controls (all p < 0.05). The percentages of both CD4+CD25highFoxP3+ and CD4+CD25highCD127 Treg lymphocytes were markedly decreased in asthmatic patients with and without steroid treatment than those in controls (all p < 0.05). The elevated IL-38 concentration negatively correlated with the percentage of Treg lymphocytes in asthmatic patients with high level (>40 ng/mL) of periostin (p < 0.05). Although the comparable mRNA levels of IL-38 and its receptor IL-36R were found between patients and controls, the mRNA level of IL-38 positively correlated with IL-36R and negatively correlated with IL-10 in all asthmatic patients (both p < 0.05). The percentage of CD4+CD25+CD134+ activated T lymphocytes was also significantly higher in asthmatic patients with steroid treatment than those in controls (p < 0.05). This cross-sectional study demonstrated that the overexpression of circulating IL-38 may play a role in the immunopathogenesis in asthma. Full article
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201 KiB  
Article
Hyper IgE in Childhood Eczema and Risk of Asthma in Chinese Children
by Chantel Ng, Kam Lun Hon, Jeng Sum Charmaine Kung, Nga Hin Pong, Ting-Fan Leung and Chun Kwok Wong
Molecules 2016, 21(6), 753; https://doi.org/10.3390/molecules21060753 - 10 Jun 2016
Cited by 12 | Viewed by 5916
Abstract
Background: Atopic eczema is a common childhood disease associated with high IgE and eosinophilia. We characterized the clinical features associated with hyper-IgE (defined as IgE > 2000 IU/L) in eczema. Methods: Nottingham Eczema Severity Score (NESS), family and personal history of atopy, [...] Read more.
Background: Atopic eczema is a common childhood disease associated with high IgE and eosinophilia. We characterized the clinical features associated with hyper-IgE (defined as IgE > 2000 IU/L) in eczema. Methods: Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test (SPT) for common food and aeroallergens, highest serum IgE ever and eosinophil counts were evaluated in 330 children eczema patients. Childhood-NESS (NESS performed at <10 years of age) and adolescent-NESS (NESS performed at >10 years of age) were further analyzed. Results: IgE correlated with NESS (spearman coefficient 0.35, p < 0.001) and eosinophil percentage (spearman coefficient 0.56, p = 0.001). Compared with IgE ≤ 2000IU/L (n = 167), patients with hyper-IgE (n = 163) were associated with male gender (p = 0.002); paternal atopy (p = 0.026); personal history of atopic rhinitis (p = 0.016); asthma (p < 0.001); dietary avoidance (p < 0.001); use of wet wrap (p < 0.001); traditional Chinese medicine use (TCM, p < 0.001); immunomodulant use (azathioprine or cyclosporine, p < 0.001); skin prick sensitization by dust mites (p < 0.001), cats (p = 0.012), dogs (p = 0.018), food (p = 0.002); eosinophilia (p < 0.001); more severe disease during childhood (p < 0.0001) and during adolescence (p < 0.0001), but not onset age of eczema or maternal atopy. Logistic regression showed that hyper-IgE was associated with personal history of asthma (exp(B) = 5.12, p = 0.002) and eczema severity during childhood and adolescence (p < 0.001). For patients <10 years of age, dust mite sensitization (p = 0.008) was associated with hyper-IgE. For patients >10years of age, food allergen sensitization was associated with hyper-IgE (p = 0.008). Conclusions: Hyper-IgE is independently associated with asthma, more severe atopy and more severe eczema during childhood and adolescence. IgE > 2000 IU/L may be a tool to aid prognostication of this chronic relapsing dermatologic disease and its progression to asthma. Full article
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Article
What Characteristics Confer Proteins the Ability to Induce Allergic Responses? IgE Epitope Mapping and Comparison of the Structure of Soybean 2S Albumins and Ara h 2
by Youngshin Han, Jing Lin, Ludmilla Bardina, Galina A. Grishina, Chaeyoon Lee, Won Hee Seo and Hugh A. Sampson
Molecules 2016, 21(5), 622; https://doi.org/10.3390/molecules21050622 - 12 May 2016
Cited by 20 | Viewed by 7290
Abstract
Ara h 2, a peanut 2S albumin, is associated with severe allergic reactions, but a homologous protein, soybean 2S albumin, is not recognized as an important allergen. Structural difference between these proteins might explain this clinical discrepancy. Therefore, we mapped sequential epitopes and [...] Read more.
Ara h 2, a peanut 2S albumin, is associated with severe allergic reactions, but a homologous protein, soybean 2S albumin, is not recognized as an important allergen. Structural difference between these proteins might explain this clinical discrepancy. Therefore, we mapped sequential epitopes and compared the structure of Ara h 2, Soy Al 1, and Soy Al 3 (Gly m 8) to confirm whether structural differences account for the discrepancy in clinical responses to these two proteins. Commercially synthesized peptides covering the full length of Ara h 2 and two soybean 2S albumins were analyzed by peptide microarray. Sera from 10 patients with peanut and soybean allergies and seven non-atopic controls were examined. The majority of epitopes in Ara h 2 identified by microarray are consistent with those identified previously. Several regions in the 2S albumins are weakly recognized by individual sera from different patients. A comparison of allergenic epitopes on peanut and soybean proteins suggests that loop-helix type secondary structures and some amino acids with a large side chain including lone electron pair, such as arginine, glutamine, and tyrosine, makes the peptides highly recognizable by the immune system. By utilizing the peptide microarray assay, we mapped IgE epitopes of Ara h 2 and two soybean 2S albumins. The use of peptide microarray mapping and analysis of the epitope characteristics may provide critical information to access the allergenicity of food proteins. Full article
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1049 KiB  
Article
Aberrant Expression of Bacterial Pattern Recognition Receptor NOD2 of Basophils and Microbicidal Peptides in Atopic Dermatitis
by Chun-Kwok Wong, Ida Miu-Ting Chu, Kam-Lun Hon, Miranda Sin-Man Tsang and Christopher Wai-Kei Lam
Molecules 2016, 21(4), 471; https://doi.org/10.3390/molecules21040471 - 11 Apr 2016
Cited by 15 | Viewed by 6075
Abstract
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease, associated with basophil infiltration into skin lesions and Staphylococcus aureus (S. aureus)-induced inflammation. Pattern recognition receptors (PRRs), including microbicidal peptide human neutrophil α-defensins (HNP) and dermcidin, can exert immunomodulating activity in [...] Read more.
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease, associated with basophil infiltration into skin lesions and Staphylococcus aureus (S. aureus)-induced inflammation. Pattern recognition receptors (PRRs), including microbicidal peptide human neutrophil α-defensins (HNP) and dermcidin, can exert immunomodulating activity in innate immunity and skin inflammation. We investigated the plasma concentration of HNP and dermcidin, the expression of bacterial toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors of basophils and plasma concentration and ex vivo induction of AD-related inflammatory cytokines and chemokines using ELISA and flow cytometry, in AD patients and control subjects. Plasma concentrations of HNP, dermcidin and AD-related Th2 chemokines CCL17, CCL22 and CCL27 were significantly elevated in AD patients compared with controls (all p < 0.05). Plasma concentrations of CCL27 and CCL22 were found to correlate positively with SCORing atopic dermatitis (SCORAD), objective SCORAD, % area affected, lichenification and disease intensity, and CCL27 also correlated positively with pruritus in AD patients (all p < 0.05). Protein expressions of NOD2 but not TLR2 of basophils were significantly down-regulated in AD patients compared with controls (p = 0.001). Correspondingly, there were lower ex vivo % inductions of allergic inflammatory tumor necrosis factor-α, IL-6 and CXCL8 from peripheral blood mononuclear cells upon NOD2 ligand S. aureus derived muramyl dipeptide stimulation in AD patients comparing with controls. The aberrant activation of bacterial PRRs of basophils and anti-bacterial innate immune response should be related with the allergic inflammation of AD. Full article
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Review

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573 KiB  
Review
Regulation of T Cell Activation and Differentiation by Extracellular Vesicles and Their Pathogenic Role in Systemic Lupus Erythematosus and Multiple Sclerosis
by Cristina Ulivieri and Cosima T. Baldari
Molecules 2017, 22(2), 225; https://doi.org/10.3390/molecules22020225 - 02 Feb 2017
Cited by 22 | Viewed by 8555
Abstract
How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs) in the lymph nodes migrate and [...] Read more.
How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs) in the lymph nodes migrate and infiltrate into the target tissues where their reactivation by peripheral tissue antigen is a prerequisite for effector cytokine production and tissue destruction. The target tissue microenvironment, as well as the local microenvironment at the immune synapse formed by T cells that encounter cognate antigen presenting cells (APCs) shave recently emerged as critical factors in shaping the differentiation and function of self-reactive effector T cells, providing the signals required for their activation in the form of the self-antigen and cytokine milieu. Moreover, depending on the specific microenvironment, self-reactive effector T cells have the ability to change their phenotype, especially Th17 and regulatory T (Treg) cells, which are characterized by the highest instability. In this context, cell-derived extracellular vesicles, i.e., vesicles carrying cytosolic proteins and nucleic acids protected by a phospholipid bilayer, as well as membrane-associated proteins, with the ability to spread throughout the body by means of biological fluids, are emerging as key mediators in intercellular communications and in the modulation of the microenvironment. In this review, we will discuss recent findings implicating extracellular vesicles (EVs) at different steps of CD4+ T cell differentiation to specific effectors, with a focus on the Th17/Treg balance and its alterations in systemic lupus erythematosus and multiple sclerosis. Full article
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768 KiB  
Review
Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders
by Patrizia Fasching, Martin Stradner, Winfried Graninger, Christian Dejaco and Johannes Fessler
Molecules 2017, 22(1), 134; https://doi.org/10.3390/molecules22010134 - 14 Jan 2017
Cited by 180 | Viewed by 21503
Abstract
A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of [...] Read more.
A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders. This review aims to summarize recent data and advances in targeted therapeutic modification of the Th17/Treg-balance, as well as information on the efficacy of candidate therapeutics with respect to the treatment of autoimmune diseases. Full article
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978 KiB  
Review
Dysregulation of Cell Death and Its Epigenetic Mechanisms in Systemic Lupus Erythematosus
by Haijing Wu, Siqi Fu, Ming Zhao, Liwei Lu and Qianjin Lu
Molecules 2017, 22(1), 30; https://doi.org/10.3390/molecules22010030 - 27 Dec 2016
Cited by 28 | Viewed by 12676
Abstract
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease involving multiple organs and tissues, which is characterized by the presence of excessive anti-nuclear autoantibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. Increasing evidence has shown that the [...] Read more.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease involving multiple organs and tissues, which is characterized by the presence of excessive anti-nuclear autoantibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. Increasing evidence has shown that the genetic susceptibilities and environmental factors-induced abnormalities in immune cells, dysregulation of apoptosis, and defects in the clearance of apoptotic materials contribute to the development of SLE. As the main source of auto-antigens, aberrant cell death may play a critical role in the pathogenesis of SLE. In this review, we summarize up-to-date research progress on different levels of cell death—including increasing rate of apoptosis, necrosis, autophagy and defects in clearance of dying cells—and discuss the possible underlying mechanisms, especially epigenetic modifications, which may provide new insight in the potential development of therapeutic strategies for SLE. Full article
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