Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.220
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
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.
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.