Journal article
Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation
Cell reports (Cambridge), Vol.29(10), pp.3073-3086.e5
12/03/2019
DOI: 10.1016/j.celrep.2019.11.010
PMCID: PMC6914223
PMID: 31801074
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.
Human genetic studies implicate IL-27 in the pathogenesis of type 1 diabetes (T1D). Ciecko et al. demonstrate that IL-27 signaling in T cells changes the balance of regulatory and effector subsets and is critical for T1D development as well as lacrimal and salivary gland inflammation in NOD mice.
Details
- Title: Subtitle
- Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation
- Creators
- Ashley E. Ciecko - Medical College of WisconsinBardees Foda - Medical College of WisconsinJennifer Y. Barr - Roy J. and Lucille A. Carver College of MedicineSheela Ramanathan - Université de SherbrookeMark A. Atkinson - University of FloridaDavid V. Serreze - Jackson LaboratoryAron M. Geurts - Medical College of WisconsinScott M. Lieberman - University of IowaYi-Guang Chen - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.29(10), pp.3073-3086.e5
- DOI
- 10.1016/j.celrep.2019.11.010
- PMID
- 31801074
- PMCID
- PMC6914223
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: EY027731, DK118786, DK097605, DK46266, DK 95735, OD020351, DK107541, DK097605, AI125879, DK121747; name: Children’s Miracle Network; DOI: 10.13039/100002570, name: American Association of Immunologists; DOI: 10.13039/100015515, name: Carver College of Medicine; DOI: 10.13039/100011343, name: Holden Comprehensive Cancer Center; name: Iowa City Veterans Administration Medical Center; DOI: 10.13039/100000097, name: National Center for Research Resources; DOI: 10.13039/100000002, name: NIH, award: 1 S10 OD016199-01A1
- Language
- English
- Date published
- 12/03/2019
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984354005402771
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