A complex auxiliary: IL-17/Th17 signaling during type 1 diabetes progression. (January 2019)

• Record Type: Journal Article
• Authors: Zheng, Zihan; Zheng, Feng
• Is Part Of: Molecular immunology. Volume 105(2019:Jan.)
• Page Start: 16
• Page End: 31
• Publication Date: 2019-01
• Subjects: T1D -- Th17 -- IL-17 -- DKD -- Diabetic complications; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.11.007
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: T1D is an autoimmune disease in which both islet-intrinsic defects and deregulation of immune cell are present. Th17/IL17 increases have been linked to T1D onset and may impact islets. Emerging bulk and single-cell transcriptomics data demonstrate that islets may receive IL-17 signal directly. IL-17 may contribute to signaling events in distal tissues to influence disease progressioncomplications. Abstract: Type 1 diabetes (T1D) is an autoimmune disease centered around the loss of the beta cells of the islets of Langerhans, and consequent inability of the islets to produce the insulin necessary to maintain glycemic control. While most therapeutic approaches have been centered on insulin replacement, newer approaches to target the underlying immune response have become an area of focus. However, the immune landscape in T1D is extremely complex, and the roles played by individual cytokines during disease progression are incompletely understood, making the development of immunotherapies very difficult. In this review, we discuss the complex auxiliary role played by IL-17, both around the islet and in peripheral tissues such as the gut and kidney, which might influence T1D progression. Through our re-analysis of the key factors involved IL-17 signaling in recently published single-cell sequencing and sorted-cell bulk sequencing datasets, we find supporting evidence for the general existence of the signaling apparatus in islet endocrine cells. We also explore the emerging evidence of IL-17 serving as an influential factor in diabetic complications that affect distal tissues. While anti-IL-17 therapies are emerging as an option for psoriasis and other autoimmune disorders, we highlight here a number of questions that would need to be addressed before their potential applicability to treating T1D can be fully evaluated.