IL-17 is expressed on beta and alpha cells of donors with type 1 and type 2 diabetes. Issue 123 (September 2021)

• Record Type: Journal Article
• Authors: Rajendran, Sakthi; Quesada-Masachs, Estefania; Zilberman, Samuel; Graef, Madeleine; Kiosses, William B.; Chu, Tiffany; Benkahla, Mehdi A.; Lee, Jae-Hyun Mason; von Herrath, Matthias
• Is Part Of: Journal of autoimmunity. Issue 123(2021)
• Publication Date: 2021-09
• Subjects: IL-17 -- Type 1 diabetes -- Type 2 diabetes -- Islets -- Beta cells -- Alpha cells; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2021.102708
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Purpose: IL-17 is an important effector cytokine driving immune-mediated destruction in autoimmune diseases such as psoriasis. Blockade of the IL-17 pathway after the initiation of insulitis was effective in delaying or preventing the onset of type 1 diabetes (T1D) in rodent models. Expression of IL-17 transcripts in islets from a donor with recent-onset T1D has been reported, however, studies regarding IL-17 protein expression are lacking. We aimed to study whether IL-17 is being expressed in the islets of diabetic donors. Methods: We stained human pancreatic tissues from non-diabetic (n = 5), auto-antibody positive (aab+) (n = 5), T1D (n = 6) and T2D (n = 5) donors for IL-17, Insulin, and Glucagon, and for CD45 in selected cases. High resolution images were acquired with Zeiss laser scanning confocal microscope LSM780 and analyzed with Zen blue 2.3 software. Cases stained for CD45 were also acquired with widefield slide scanner and analyzed with QuPath software. Results: We observed a clear cytoplasmic staining for IL-17 in insulin-containing islets of donors with T1D and T2D, accounting for an average of 7.8 ± 8.4% and 14.9 ± 16.8% of total islet area, respectively. Both beta and alpha cells were sources of IL-17, but CD45 + cells were not a major source of IL-17 in those donors. Expression of IL-17 was reduced in islets of non-diabetic donors, aab+ donors and in insulin-deficient islets of donors with T1D. Conclusion: Our finding that IL-17 is expressed in islets of donors with T1D or T2D is quite intriguing and warrants further mechanistic studies in human islets to understand the role of IL-17 in the context of metabolic and immune stress in beta cells. Highlights: IL-17 is expressed in insulin containing islets of donors with type 1 (T1D) and type 2 diabetes (T2D). Both beta and alpha cells can express IL-17 in donors with T1D and T2D. Donors with T2D have the highest expression of IL-17 in the islets, mainly present in beta and alpha cells.