Journal article
An interleukin-27 centered cytokine circuit regulates macrophage and T cell interactions in autoimmune diabetes
iScience, Vol.28(10), 113537
10/2025
DOI: 10.1016/j.isci.2025.113537
PMCID: PMC12494592
PMID: 41050931
Abstract
Summary
In the non-obese diabetic (NOD) mouse model of autoimmune diabetes, interleukin (IL)-27 stimulates interferon γ (IFNγ) production by CD4 and CD8 T cells and is essential for disease development. Here, we tested the role of IL-27 in cellular communication. Single-cell RNA sequencing and T cell adoptive transfer showed that IL-27 intrinsically controlled the differentiation of islet-infiltrating CD4 T cells by driving them toward an IL-21+ Th1 phenotype. Consequently, IL-27 signaling in CD4 T cells was important for BATF and granzyme B expression in islet CD8 T effectors. BATF overexpression increased the diabetogenic potential of β cell autoreactive CD8 T cells lacking help from CD4 T cell-derived IL-21. Macrophages were the main source of IL-27 in the islets, whose expression correlated with T cell infiltration. IFNγ and CD40 signaling conferred by activated T cells induced macrophage IL-27 production. Collectively, our findings reveal a role for IL-27 in orchestrating interconnected positive feedback loops involving CD4 T cells, CD8 T cells, and macrophages in autoimmune diabetes.
Details
- Title: Subtitle
- An interleukin-27 centered cytokine circuit regulates macrophage and T cell interactions in autoimmune diabetes
- Creators
- Ashley E. CieckoRabia NabiAmber DrewekDavid M. SchauderPavel N. ZakharovXiaoxiao WanScott M. LiebermanWeiguo CuiMartin J. HessnerChien-Wei LinYi-Guang Chen
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.28(10), 113537
- DOI
- 10.1016/j.isci.2025.113537
- PMID
- 41050931
- PMCID
- PMC12494592
- NLM abbreviation
- iScience
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Publisher
- CELL PRESS
- Grant note
- NIH: DK118786, DK108557, AI144360, DK107541, DK121747, DK097605
The authors would like to thank Ross Kedl for providing C57BL/6 IL-27p28-eGFP mice. We would like to thank Galina Petrova at the Children's Research Institute Flow Cytometry Core for excellent technical assistance. This work was supported by NIH grants to A.E.C. (DK118786) , D.M.S. (DK108557) , and Y.-G.C. (AI144360, DK107541, DK121747, and DK097605) .
- Language
- English
- Electronic publication date
- 09/10/2025
- Date published
- 10/2025
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984964743402771
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