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Immunity and Inflammation in Health and Disease: Insights into Sex-Based Mechanisms and Their Modifiers

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 June 2023) | Viewed by 4748

Special Issue Editors

Dr. Rita Del Pinto

E-Mail Website
Guest Editor
Internal Medicine and Nephrology Unit, Department of Life, Health & Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Interests: hypertension; blood pressure variability; metabolism; vitamin D; oxidative stress; dysbiosis; inflammation
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Theresa Torres Pizarro

E-Mail Website
Co-Guest Editor
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Interests: medicine; immunology and microbiology; mucosal immunity; inflammatory bowel disease (IBD); sex hormones

Special Issue Information

Dear Colleagues,

In recent years, evidence has accumulated in support of the role of biological sex in the functions of the immune system and the related implications in health and disease states throughout life. Sex differences occur in both innate and adaptive immune responses and are highly evolutionary preserved, typically manifesting as stronger innate and adaptive immune responses in females compared with males. Although resulting in faster clearance of pathogens and greater vaccine efficacy in females than in males, these differences also contribute to the increased susceptibility to and severity of inflammatory and autoimmune diseases in the former. Experimental evidence suggests that sex hormone signaling modulates immunocompetence in individuals with predisposing genetic and environmental exposure, yet the underlying mechanisms have not been fully understood. The mechanistic involvement of both genes and hormones is grounded on the observation that some sex-based immunological differences are evident throughout life, whereas others are only apparent in the fertility age range. The impact of nutrition, and the composition of human virome and microbiome in the development and functioning of the immune system in males and females is intriguing and carries possible therapeutic implications that are under investigation. Relevant to environmental influences, gender-related behaviours can also impact on exposure to microorganisms, access to healthcare, or health-seeking behaviours, thereby affecting the course of immune-mediated diseases. This Special Issue is dedicated to the understanding of sex-based molecular events in acute and chronic inflammation and immune-driven diseases, welcoming studies that help clarify the role of biological sex in identifying the high-risk phenotype, the potential influence of gender-based factors on the disease course, and the possible targets for more effective prevention and treatment of immune system-related diseases.

Dr. Rita Del Pinto
Prof. Dr. Theresa Torres Pizarro
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

  • biological sex
  • sex hormones
  • genetics
  • environment
  • gender
  • microbiome
  • innate immunity
  • adaptive immunity
  • inflammatory diseases
  • immune-mediated diseases

Published Papers (2 papers)

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Research

16 pages, 4774 KiB  
Article
Benzo[a]pyrene Exposure Reduces Cell-Type Diversity and Stimulates Sex-Biased Damage Pathways in End Organs of Lupus-Prone Mice
by Runqi Zhu, Kameron Kennicott and Yun Liang
Int. J. Mol. Sci. 2023, 24(7), 6163; https://doi.org/10.3390/ijms24076163 - 24 Mar 2023
Cited by 1 | Viewed by 1930
Abstract
Studies indicate that genetic factors only account for approximately thirty percent of all autoimmune diseases, while the rest of autoimmune pathogenesis is attributed to environmental factors including toxic chemicals. To understand if and how environmental pollutants trigger autoimmunity, we investigated the effect of [...] Read more.
Studies indicate that genetic factors only account for approximately thirty percent of all autoimmune diseases, while the rest of autoimmune pathogenesis is attributed to environmental factors including toxic chemicals. To understand if and how environmental pollutants trigger autoimmunity, we investigated the effect of benzo[a]pyrene (BaP) exposure on the development of autoimmune phenotypes in the lupus-prone MRL strain. The exposure of MRL mice to BaP over the course of 8 weeks before lupus onset resulted in total body weight loss in males, while marginal changes in anti-dsDNA levels occurred. Multi-organ analyses of BaP-treated and control MRL mice suggested that the kidney is a major organ directly affected by the metabolism of benzene-containing compounds, with increased expression of BaP-target genes including Cyp4b1 and Hao2. Intriguingly, spatial transcriptomic data showed that BaP caused a drastic reduction in cell-type diversity in both the kidneys and spleen of MRL mice. Further analysis of the molecular pathways affected suggested a sex-biased effect of BaP treatment, with the upregulated expression of angiogenesis genes in the lungs and an increased deposition of C3 in the kidneys of male mice. While SLE is more common in women, the disease is more severe in male patients, with an increased risk of disease progression to renal failure and lung cancer. Our results reveal sex-biased molecular pathways stimulated by BaP which may help explain the increased likelihood of end organ damage in males with lupus. Full article
(This article belongs to the Special Issue Immunity and Inflammation in Health and Disease: Insights into Sex-Based Mechanisms and Their Modifiers)
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17 pages, 27408 KiB  
Article
Colitis Induces Sex-Specific Intestinal Transcriptomic Responses in Mice
by Linnea Hases, Madeleine Birgersson, Rajitha Indukuri, Amena Archer and Cecilia Williams
Int. J. Mol. Sci. 2022, 23(18), 10408; https://doi.org/10.3390/ijms231810408 - 8 Sep 2022
Cited by 6 | Viewed by 2386
Abstract
There are significant sex differences in colorectal cancer (CRC), including in incidence, onset, and molecular characteristics. Further, while inflammatory bowel disease (IBD) is a risk factor for CRC in both sexes, men with IBD have a 60% higher risk of developing CRC compared [...] Read more.
There are significant sex differences in colorectal cancer (CRC), including in incidence, onset, and molecular characteristics. Further, while inflammatory bowel disease (IBD) is a risk factor for CRC in both sexes, men with IBD have a 60% higher risk of developing CRC compared to women. In this study, we investigated sex differences during colitis-associated CRC (CAC) using a chemically induced CAC mouse model. The mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) and followed for 9 and 15 weeks. We performed RNA-sequencing of colon samples from males (n = 15) and females (n = 15) to study different stages of inflammation and identify corresponding transcriptomic sex differences in non-tumor colon tissue. We found a significant transcriptome response to AOM/DSS treatment in both sexes, including in pathways related to inflammation and cell proliferation. Notably, we found a stronger response in males and that male-specific differentially expressed genes were involved in NFκB signaling and circadian rhythm. Further, an overrepresented proportion of male-specific gene regulations were predicted to be targets of Stat3, whereas for females, targets of the glucocorticoid receptor (Gr/Nr3c1) were overrepresented. At 15 weeks, the most apparent sex difference involved genes with functions in T cell proliferation, followed by the regulation of demethylases. The majority of sex differences were thus related to inflammation and the immune system. Our novel data, profiling the transcriptomic response to chemically induced colitis and CAC, indicate clear sex differences in CRC initiation and progression. Full article
(This article belongs to the Special Issue Immunity and Inflammation in Health and Disease: Insights into Sex-Based Mechanisms and Their Modifiers)
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