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Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0
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Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 16340

Special Issue Editors

Prof. Dr. Krzysztof Bryniarski

E-Mail Website
Guest Editor
Department of Immunology, Jagiellonian University Medical College, 18 Czysta St., 31-121 Krakow, Poland
Interests: contact and delayed-type hypersensitivity; exosomes; extracellular vesicles; immune regulation; immune tolerance; mechanisms underlying hypersensitivity reactions; miRNAs; mouse models of allergy and autoimmunity
Special Issues, Collections and Topics in MDPI journals
Dr. Katarzyna Nazimek

E-Mail Website
Guest Editor
Department of Immunology, Jagiellonian University Medical College, 18 Czysta St., 31-121 Krakow, Poland
Interests: contact and delayed-type hypersensitivity; exosomes; extracellular vesicles; immune regulation via miRNAs; immune tolerance; macrophages; mechanisms underlying hypersensitivity reactions; mouse models of allergy and autoimmunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to introduce to you this Special Issue of the Molecular Immunology Section of International Journal of Molecular Sciences on “Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0”.

Extracellular vesicles (EVs), such as exosomes, receive special attention due to their involvement in systemic intercellular communication and their capability of delivering various immune regulatory molecules, including non-coding RNAs. This EV-mediated transfer of genetically encoded information is unprecedented and paradigm breaking. Increasing the prevalence of allergic and autoimmune diseases urges researchers and clinicians to search for new and efficient treatments. Accordingly, recent advances in understanding complex functions of EVs in hypersensitivity reactions make them promising candidates for creating a new pathway in specific immunotherapy, firstly by complimenting the existing treatments to reduce the toxic side effects and increase the specificity, and secondly, by altering the unwanted immune responses underlying allergic or autoimmune disorders.

Therefore, this Special Issue is aimed at presenting the comprehensive studies on the functions of EVs in allergies and autoimmune diseases, as well as in the regulation of immune responses. We will also gladly accept the articles describing newly discovered EV-based mechanisms of induction of immune tolerance and uncovering the immunotherapeutic potential of EVs in allergies and autoimmunity.

We cordially invite all interested researchers to submit original and review articles covering relevant basic research findings and the clinical aspects of EVs’ functions to make the “Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation” Special Issue a platform for sharing experiences between researchers and clinicians.  

Please accept our sincere thanks in advance for choosing this publishing opportunity.

Prof. Dr. Krzysztof Bryniarski
Dr. Katarzyna Nazimek
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Allergy
  • Autoimmune disease
  • Extracellular vesicles
  • Exosomes
  • Hypersensitivity
  • Immune modulation
  • Immune regulation
  • Immune tolerance
  • miRNA
  • Research models of allergy and autoimmunity.

Related Special Issue

Published Papers (6 papers)

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Editorial

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3 pages, 179 KiB  
Editorial
Advances in the Current Understanding of the Role of Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation
by Krzysztof Bryniarski and Katarzyna Nazimek
Int. J. Mol. Sci. 2022, 23(22), 14311; https://doi.org/10.3390/ijms232214311 - 18 Nov 2022
Viewed by 1050
Abstract
Cells release extracellular vesicles (EVs), such as exosomes and microvesicles, both under physiological and pathological conditions, making EV-dependent signaling cascades a very precise system of intercellular communication [...] Full article
(This article belongs to the Special Issue Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0)

Research

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13 pages, 1621 KiB  
Article
Enhanced Extracellular Transfer of HLA-DQ Activates CD3+ Lymphocytes towards Compromised Treg Induction in Celiac Disease
by Michael Hudec, Iva Juříčková, Kamila Riegerová, Saak V. Ovsepian, Marie Černá and Valerie Bríd O’Leary
Int. J. Mol. Sci. 2022, 23(11), 6102; https://doi.org/10.3390/ijms23116102 - 29 May 2022
Cited by 4 | Viewed by 2029
Abstract
Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) [...] Read more.
Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) on T lymphocytes. This fundamental mechanism of adaptive immunity has broadened upon recognition of extracellular exosomal MHC, raising awareness of an alternative means for antigen presentation. This study demonstrates that conditioned growth media (CGM) previously exposed to monocyte-derived dendritic cells from CeD significantly downregulates the CD3+ lineage marker of control T cells. Such increased activation was reflected in their elevated IL-2 secretion. Exosome localization motif identification and quantification within HLA-DQA1 and HLA-DQB1 transcripts highlighted their significant prevalence within HLA-DQB1 alleles associated with CeD susceptibility. Flow cytometry revealed the strong correlation between HLA-DQ and the CD63 exosomal marker in T cells exposed to CGM from MoDCs sourced from CeD patients. This resulted in lower concentrations of CD25+ CD127− T cells, suggestive of their compromised induction to T-regulatory cells associated with CeD homeostasis. This foremost comparative study deciphered the genomic basis and extracellular exosomal effects of HLA transfer on T lymphocytes in the context of CeD, offering greater insight into this auto-immune disease. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0)
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Graphical abstract

20 pages, 2874 KiB  
Article
The Extracellular Vesicles from the Commensal Staphylococcus Epidermidis ATCC12228 Strain Regulate Skin Inflammation in the Imiquimod-Induced Psoriasis Murine Model
by Fernando Gómez-Chávez, Carlos Cedillo-Peláez, Luis A. Zapi-Colín, Guadalupe Gutiérrez-González, Isaí Martínez-Torres, Humberto Peralta, Leslie Chavez-Galan, Erick D. Avila-Calderón, Araceli Contreras-Rodríguez, Yaneth Bartolo-Aguilar, Sandra Rodríguez-Martínez, Mario E. Cancino-Diaz and Juan C. Cancino-Diaz
Int. J. Mol. Sci. 2021, 22(23), 13029; https://doi.org/10.3390/ijms222313029 - 2 Dec 2021
Cited by 13 | Viewed by 3488
Abstract
Extracellular vesicles (EVs) are evaginations of the cytoplasmic membrane, containing nucleic acids, proteins, lipids, enzymes, and toxins. EVs participate in various bacterial physiological processes. Staphylococcus epidermidis interacts and communicates with the host skin. S. epidermidis’ EVs may have an essential role in this [...] Read more.
Extracellular vesicles (EVs) are evaginations of the cytoplasmic membrane, containing nucleic acids, proteins, lipids, enzymes, and toxins. EVs participate in various bacterial physiological processes. Staphylococcus epidermidis interacts and communicates with the host skin. S. epidermidis’ EVs may have an essential role in this communication mechanism, modulating the immunological environment. This work aimed to evaluate if S. epidermidis’ EVs can modulate cytokine production by keratinocytes in vitro and in vivo using the imiquimod-induced psoriasis murine model. S. epidermidis’ EVs were obtained from a commensal strain (ATC12228EVs) and a clinical isolated strain (983EVs). EVs from both origins induced IL-6 expression in HaCaT keratinocyte cultures; nevertheless, 983EVs promoted a higher expression of the pro-inflammatory cytokines VEGF-A, LL37, IL-8, and IL-17F than ATCC12228EVs. Moreover, in vivo imiquimod-induced psoriatic skin treated with ATCC12228EVs reduced the characteristic psoriatic skin features, such as acanthosis and cellular infiltrate, as well as VEGF-A, IL-6, KC, IL-23, IL-17F, IL-36γ, and IL-36R expression in a more efficient manner than 983EVs; however, in contrast, Foxp3 expression did not significantly change, and IL-36 receptor antagonist (IL-36Ra) was found to be increased. Our findings showed a distinctive immunological profile induction that is dependent on the clinical or commensal EV origin in a mice model of skin-like psoriasis. Characteristically, proteomics analysis showed differences in the EVs protein content, dependent on origin of the isolated EVs. Specifically, in ATCC12228EVs, we found the proteins glutamate dehydrogenase, ornithine carbamoyltransferase, arginine deiminase, carbamate kinase, catalase, superoxide dismutase, phenol-soluble β1/β2 modulin, and polyglycerol phosphate α-glucosyltransferase, which could be involved in the reduction of lesions in the murine imiquimod-induced psoriasis skin. Our results show that the commensal ATCC12228EVs have a greater protective/attenuating effect on the murine imiquimod-induced psoriasis by inducing IL-36Ra expression in comparison with EVs from a clinical isolate of S. epidermidis. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0)
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Review

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15 pages, 849 KiB  
Review
Extracellular Vesicles—Oral Therapeutics of the Future
by Martyna Cieślik, Katarzyna Nazimek and Krzysztof Bryniarski
Int. J. Mol. Sci. 2022, 23(14), 7554; https://doi.org/10.3390/ijms23147554 - 7 Jul 2022
Cited by 11 | Viewed by 3818
Abstract
Considered an artifact just after discovery, the possibility of oral delivery of extracellular vesicles (EVs) and their functional cargos has recently gained much research attention. EVs from various sources, including edible plants, milk, bacteria and mammalian cells, have emerged as a platform for [...] Read more.
Considered an artifact just after discovery, the possibility of oral delivery of extracellular vesicles (EVs) and their functional cargos has recently gained much research attention. EVs from various sources, including edible plants, milk, bacteria and mammalian cells, have emerged as a platform for miRNA and drug delivery that seem to induce the expected immune effects locally and in distant tissues after oral administration. Such a possibility greatly expands the clinical applicability of EVs. The present review summarizes research findings that either support or deny the biological/therapeutical activity of orally administered EVs and their role in cross-species and cross-kingdom signaling. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0)
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25 pages, 857 KiB  
Review
Exosome Carrier Effects; Resistance to Digestion in Phagolysosomes May Assist Transfers to Targeted Cells; II Transfers of miRNAs Are Better Analyzed via Systems Approach as They Do Not Fit Conventional Reductionist Stoichiometric Concepts
by Philip W. Askenase
Int. J. Mol. Sci. 2022, 23(11), 6192; https://doi.org/10.3390/ijms23116192 - 31 May 2022
Cited by 6 | Viewed by 2387
Abstract
Carrier effects of extracellular vesicles (EV) like exosomes refer to properties of the vesicles that contribute to the transferred biologic effects of their contents to targeted cells. This can pertain to ingested small amounts of xenogeneic plant miRNAs and oral administration of immunosuppressive [...] Read more.
Carrier effects of extracellular vesicles (EV) like exosomes refer to properties of the vesicles that contribute to the transferred biologic effects of their contents to targeted cells. This can pertain to ingested small amounts of xenogeneic plant miRNAs and oral administration of immunosuppressive exosomes. The exosomes contribute carrier effects on transfers of miRNAs by contributing both to the delivery and the subsequent functional intracellular outcomes. This is in contrast to current quantitative canonical rules that dictate just the minimum copies of a miRNA for functional effects, and thus successful transfers, independent of the EV carrier effects. Thus, we argue here that transfers by non-canonical minute quantities of miRNAs must consider the EV carrier effects of functional low levels of exosome transferred miRNA that may not fit conventional reductionist stoichiometric concepts. Accordingly, we have examined traditional stoichiometry vs. systems biology that may be more appropriate for delivered exosome functional responses. Exosome carrier properties discussed include; their required surface activating interactions with targeted cells, potential alternate targets beyond mRNAs, like reaching a threshold, three dimensional aspects of the RNAs, added EV kinetic dynamic aspects making transfers four dimensional, and unique intracellular release from EV that resist intracellular digestion in phagolysosomes. Together these EV carrier considerations might allow systems analysis. This can then result in a more appropriate understanding of transferred exosome carrier-assisted functional transfers. A plea is made that the miRNA expert community, in collaboration with exosome experts, perform new experiments on molecular and quantitative miRNA functional effects in systems that include EVs, like variation in EV type and surface constituents, delivery, dose and time to hopefully create more appropriate and truly current canonical concepts of the consequent miRNA functional transfers by EVs like exosomes. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0)
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14 pages, 2995 KiB  
Review
Immune Modulation Using Extracellular Vesicles Encapsulated with MicroRNAs as Novel Drug Delivery Systems
by Yasunari Matsuzaka and Ryu Yashiro
Int. J. Mol. Sci. 2022, 23(10), 5658; https://doi.org/10.3390/ijms23105658 - 18 May 2022
Cited by 8 | Viewed by 2880
Abstract
Self-tolerance involves protection from self-reactive B and T cells via negative selection during differentiation, programmed cell death, and inhibition of regulatory T cells. The breakdown of immune tolerance triggers various autoimmune diseases, owing to a lack of distinction between self-antigens and non-self-antigens. Exosomes [...] Read more.
Self-tolerance involves protection from self-reactive B and T cells via negative selection during differentiation, programmed cell death, and inhibition of regulatory T cells. The breakdown of immune tolerance triggers various autoimmune diseases, owing to a lack of distinction between self-antigens and non-self-antigens. Exosomes are non-particles that are approximately 50–130 nm in diameter. Extracellular vesicles can be used for in vivo cell-free transmission to enable intracellular delivery of proteins and nucleic acids, including microRNAs (miRNAs). miRNAs encapsulated in exosomes can regulate the molecular pathways involved in the immune response through post-transcriptional regulation. Herein, we sought to summarize and review the molecular mechanisms whereby exosomal miRNAs modulate the expression of genes involved in the immune response. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation 2.0)
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