An Introduction to the Special Issue on “Cytokines and Autoimmune Diseases”

Abstract

S ince their initial discovery, interferons and subsequently the interleukins, chemokines, tumor necrosis factors, and colony stimulating factors have greatly advanced our understanding of how the immune system works. In general, while the hematopoietic cells act as hardware, cytokines serve as software that runs the immune system. Although initially thought to confer a beneficial host defensive effect, a number of studies have now established that dysregulation of immune cell function causes debilitating autoimmune diseases such as lupus, arthritis, thyroiditis, carditis, and diabetes. It is not hyperbolic to state that cytokine dysfunctions are the first step in onset of such self-reactive immune responses. In light of the central importance of cytokines to autoimmune diseases, Journal of Interferon & Cytokine Research (JICR) decided to bring a special issue comprising of reviews from several experts working in the field. Since many experts in this field are not on the JICR editorial board, I have invited Dr. Kamal D. Moudgil, Professor of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, an expert on arthritis, and Dr. Divaker Choubey, Professor, University of Cincinnati, Cincinnati, OH, an expert on lupus, to act as guest editors to help me in assembling a special issue. This effort resulted in securing 16 expert review articles, which the editors of JICR (Ganes Sen, Thomas Hamilton, and Dhan V. Kalvakolanu) decided to bring in 2 volumes. This is the first of 2 issues to be published. The overall summary of articles in this issue and a preview of the upcoming articles are reviewed in the first article by Kamal Moudgil and Divaker Choubey. The editors by no means conclude that these articles will cover the entire area of autoimmune diseases. In the future, the journal wishes to publish more expert reviews and original articles on various aspects of autoimmune diseases. With the publication of these articles, the JICR extends invitation to potential authors to submit their original research articles for publication. Before I conclude, a word about the guest editors …

Kamal Moudgil, M.D., Ph.D.

Dr. Mougil's research interests are focused on antigen processing and presentation, self-tolerance, and its impact on shaping of the self-directed T cell repertoire, and the pathogenesis and regulation of autoimmunity. Through studies based on the adjuvant-induced arthritis (AA) model of human rheumatoid arthritis, his group has made significant contributions to the understanding of the pathogenesis of autoimmunity and its regulation. Some of the earlier findings in the AA model that have had a major impact on this area of research include epitope mapping of the disease-associated antigen, mycobacterial heat-shock protein 65 (Bhsp65); demonstrating the phenomenon of diversification of T cell response to Bhsp65 during the course of arthritis and its role in regulation rather than progression of the disease process; defining the involvement of self (rat)-hsp65 in regulation of arthritis in part via driving the diversification of response to Bhsp65; identifying and validating the Wistar Kyoto rat (which has the same major histocompatibility complex haplotype as the arthritis-susceptible Lewis rat) as an arthritis-resistant rat strain, and studying the immunologic basis of susceptibility/resistance to arthritis; and showing that antibodies generated during the course of arthritis are disease-protective in nature. Some of the recent work from his laboratory is focused on defining the dynamics of cytokine responses during the course of arthritis and the novel aspects of cytokine cross-regulation in vivo; examining the balance between T helper 17 and regulatory T cells at different phases of arthritis; studying the role of antibodies against post-translationally modified antigens in the induction of arthritis; and developing novel immunomodulatory and therapeutic approaches for arthritis, including the use of cytokines and natural products. He has published over 80 peer-reviewed scientific articles in journals, written over 30 book chapters, and co-edited a textbook. He also served as an ad-hoc member of 18 review groups and a permanent member of one of the review groups of the U.S. National Institutes of Health. He currently serves on the editorial board of the journal Autoimmune Diseases and chaired scientific sessions at several international and national conferences.

Divaker Choubey, Ph.D.

Divaker Choubey is one of the first investigators who worked on the biology of the p200 family of interferon (IFN)-induced proteins, when he was in Peter Lengyel's Laboratory at the Yale University. His laboratory has been interested in the potential role of type I IFN pathway and IFN-inducible genes in systemic lupus erythematosus (SLE). Particularly, he has been interested in the role of p200-family proteins (encoded by the Ifi200-family genes) in innate and adaptive immune responses that contribute to the development of SLE. His collaborations with the Brian Kotzin's laboratory resulted in the identification of the Ifi202 gene (encoding for the p202 protein) as a candidate for lupus susceptibility gene within the New Zealand Black autoimmunity 2 interval (the Nba2 interval) on the mouse chromosome 1. Several lines of evidence from the Choubey laboratory (and those of others) in the last decade strongly suggest that the Ifi202 gene is a major genetic contributor in the Nba2 phenotype (autoantibody production and type I IFN production). Notably, studies in the Choubey laboratory have provided important molecular links between the IFN pathway and the female sex hormone estrogen/estrogen receptor (ER)α signaling. These cross-talks between the 2 signaling pathways are likely to contribute to gender bias in certain autoimmune diseases. Moreover, these studies are likely to improve the understanding of the molecular mechanisms by which the type I IFN pathway and IFN-inducible p200-family proteins contribute to lupus susceptibility in females. Alterations in expression of the p200-family proteins are associated with the development of human autoimmune diseases and inflammation-associated diseases. Currently, the Choubey laboratory is investigating the role of (1) murine Aim2 and p202 proteins in lupus susceptibility and inflammation and (2) human AIM2 and IFI16 proteins in chronic inflammation-associated prostatic diseases. Dr. Choubey published 71 articles in various top-tier journals and served as a member of several U.S. National Institutes of Health peer review study sections. He is also a member of the editorial board of JICR.

I sincerely thank Kamal and Divaker for acting as guest editors for this special issue on “cytokines and autoimmune diseases.” I also appreciate the editorial guidance of Ganes Sen and Thomas Hamilton; administrative assistance of Marieta Cepec, JICR Editorial office; and the support of Mary Ann Liebert Publishers, especially Vicki Cohn, which are critical in bringing these special issues out. I believe that readers will benefit from these expert reviews.