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Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation.
Cell Rep 2019; 29(10):3073-3086.e5CR

Abstract

Human genetic studies implicate interleukin-27 (IL-27) in the pathogenesis of type 1 diabetes (T1D), but the underlying mechanisms remain largely unexplored. To further define the role of IL-27 in T1D, we generated non-obese diabetic (NOD) mice deficient in IL-27 or IL-27Rα. In contrast to wild-type NOD mice, both NOD.Il27-/- and NOD.Il27ra-/- strains are completely resistant to T1D. IL-27 from myeloid cells and IL-27 signaling in T cells are critical for T1D development. IL-27 directly alters the balance of regulatory T cells (Tregs) and T helper 1 (Th1) cells in pancreatic islets, which in turn modulates the diabetogenic activity of CD8 T cells. IL-27 also directly enhances the effector function of CD8 T cells within pancreatic islets. In addition to T1D, IL-27 signaling in T cells is also required for lacrimal and salivary gland inflammation in NOD mice. Our study reveals that IL-27 contributes to autoimmunity in NOD mice through multiple mechanisms and provides substantial evidence to support its pathogenic role in human T1D.

Authors+Show Affiliations

Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Department of Molecular Genetics and Enzymology, National Research Centre, Dokki, Egypt.Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52240, USA.Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.Departments of Pediatrics, and Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32611, USA.The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52240, USA.Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: yichen@mcw.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31801074

Citation

Ciecko, Ashley E., et al. "Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation." Cell Reports, vol. 29, no. 10, 2019, pp. 3073-3086.e5.
Ciecko AE, Foda B, Barr JY, et al. Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation. Cell Rep. 2019;29(10):3073-3086.e5.
Ciecko, A. E., Foda, B., Barr, J. Y., Ramanathan, S., Atkinson, M. A., Serreze, D. V., ... Chen, Y. G. (2019). Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation. Cell Reports, 29(10), pp. 3073-3086.e5. doi:10.1016/j.celrep.2019.11.010.
Ciecko AE, et al. Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation. Cell Rep. 2019 Dec 3;29(10):3073-3086.e5. PubMed PMID: 31801074.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation. AU - Ciecko,Ashley E, AU - Foda,Bardees, AU - Barr,Jennifer Y, AU - Ramanathan,Sheela, AU - Atkinson,Mark A, AU - Serreze,David V, AU - Geurts,Aron M, AU - Lieberman,Scott M, AU - Chen,Yi-Guang, PY - 2019/06/19/received PY - 2019/09/26/revised PY - 2019/11/04/accepted PY - 2019/12/5/entrez PY - 2019/12/5/pubmed PY - 2019/12/5/medline KW - IL-27 KW - IL-27Ra KW - NOD mouse KW - Sjögren syndrome KW - T cells KW - T-bet KW - autoimmunity KW - insulitis KW - type 1 diabetes SP - 3073 EP - 3086.e5 JF - Cell reports JO - Cell Rep VL - 29 IS - 10 N2 - Human genetic studies implicate interleukin-27 (IL-27) in the pathogenesis of type 1 diabetes (T1D), but the underlying mechanisms remain largely unexplored. To further define the role of IL-27 in T1D, we generated non-obese diabetic (NOD) mice deficient in IL-27 or IL-27Rα. In contrast to wild-type NOD mice, both NOD.Il27-/- and NOD.Il27ra-/- strains are completely resistant to T1D. IL-27 from myeloid cells and IL-27 signaling in T cells are critical for T1D development. IL-27 directly alters the balance of regulatory T cells (Tregs) and T helper 1 (Th1) cells in pancreatic islets, which in turn modulates the diabetogenic activity of CD8 T cells. IL-27 also directly enhances the effector function of CD8 T cells within pancreatic islets. In addition to T1D, IL-27 signaling in T cells is also required for lacrimal and salivary gland inflammation in NOD mice. Our study reveals that IL-27 contributes to autoimmunity in NOD mice through multiple mechanisms and provides substantial evidence to support its pathogenic role in human T1D. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/31801074/Interleukin-27_Is_Essential_for_Type_1_Diabetes_Development_and_Sjögren_Syndrome-like_Inflammation L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(19)31481-0 DB - PRIME DP - Unbound Medicine ER -