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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2018; 9(12): 220-225
Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.220
Unexpected alliance between syndecan-1 and innate-like T cells to protect host from autoimmune effects of interleukin-17
Anil Kumar Jaiswal, Mohanraj Sadasivam, Abdel Rahim A Hamad
Anil Kumar Jaiswal, Department of Pathobiology, Auburn University, Auburn, AL 36849, United States
Mohanraj Sadasivam, Abdel Rahim A Hamad, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, United States
Author contributions: All authors contributed to conception and writing of this article.
Conflict-of-interest statement: Authors declare no coflict of interest.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Abdel Rahim A Hamad, PhD, Associate Professor, Department of Pathology, School of Medicine, Johns Hopkins University, Ross 66G, 720 Rutland Ave, Baltimore, MD 21205, United States. ahamad@jhmi.edu
Telephone: +1-410-6143021 Fax: +1-410-6143548
Received: September 1, 2018
Peer-review started: September 3, 2018
First decision: October 16, 2018
Revised: October 23, 2018
Accepted: November 26, 2018
Article in press: November 26, 2018
Published online: December 15, 2018
Abstract

Innate-like T cells, namely natural killer T (NKT) and γδ T cells, play critical roles in linking innate and adaptive immune responses through rapid production of cytokines. Prominent among these cytokines is interleukin-17 (IL-17), which is a potent proinflammatory cytokine that plays a critical role in host defense against fungi and extracellular bacteria. However, excessive IL-17-production promotes autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. IL-17 has also been implicated in regulating body fat, which is highly relevant given rises in obesity and type 2 diabetes. NKT cells, γδ T cells and mucosal-associated invariant T cells (MAIT) are the major sources of IL-17 involved in protection of mucosal surfaces from opportunistic infections and causing autoimmunity when become dysregulated. Given the pathogenic effects of IL-17, efforts have been directed towards understanding mechanisms that guard against IL-17 overproduction. One novel potent mechanism is mediated by the heparan sulfate proteoglycan, syndecan-1 (sdc1), which is selectively expressed by IL-17-producing subsets of NKT and γδ T cells. This unexpected role for sdc1 is uncovered by analysis of NKT and γδ T cells in sdc1-deficient mice. In this mini-review, we discuss selective expression of sdc1 by these innate T cells and consequences of its absence on IL-17 homeostasis and pathological implications.

Keywords: Natural killer T cell, Natural killer T 17 cells, Tγδ17 cells, Syndecan-1, Interleukin-17

Core tip: Interleukin-17 (IL-17) is a potent proinflammatory cytokine that plays a critical role in host defense against fungi and extracellular bacteria. Excessive production of IL-17, however, has been implicated in pathogenesis of many autoimmune diseases. Our recent findings show that natural killer T (NKT) cells and γδ T cells employ syndecan-1 (sdc1), a heparan sulfate proteoglycan that is predominantly expressed by epithelia, to prevent out of control expansion of IL-17-producing subsets of NKT (NKT17) cell and γδ (Tγδ17) cells. In this mini-review, we highlight these findings and briefly discuss their significance for developing new strategies to prevent IL-17-mediated autoimmme diseases.