Interleukin-27 is essential for type 1 diabetes development and Sjögren syndrome-like inflammation

Ciecko, Ashley E.; Foda, Bardees M.; Barr, Jennifer; Ramanathan, Sheela; Atkinson, Mark A.; Serreze, David; Geurts, Aron M.; Chen, Yi-Guang

doi:10.1016/j.celrep.2021.108725

Cited by 4 publications

(12 citation statements)

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“…4), indicating a crucial for this transcription factor in autoimmune diabetes manifestation. In addition to these upregulated genes, the steady-state levels of several genes implicated in T1D such as Il4 [41], Il18 [42], and Il27p28 [43] were also diminished in TSA-treated spleen (Fig. 2).…”

Section: Discussionmentioning

confidence: 97%

Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection

Jayaraman

Arianas

Jayaraman

2021

Preprint

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We have previously demonstrated that treatment of female NOD mice with the histone deacetylase inhibitor Trichostatin A (TSA) bestowed irreversible protection against diabetes. Herein we show that drug treatment diminished the infiltration of the pancreas with CD4+ and CD8+ T cells and Ly-6C+ monocytes. Significantly, TSA administration selectively repressed the expression of a set of genes exaggerated during diabetes and constitutively expressed primarily in the spleen and rarely in the pancreas. These genes encode lymphokines, macrophage-associated determinants, and transcription factors. Although the copy numbers of many histone deacetylases increased during diabetes in the spleen and pancreas, only those upregulated in the spleen were rendered sensitive to repression by TSA treatment. The T lymphocytes derived from drug-treated donors displayed diminished diabetogenic potential following transfer into immunodeficient NOD.scid mice. In the immunocompromised recipients, diabetes caused by the transfer of activated T lymphocytes from untreated diabetic mice was hampered by the co-transfer of highly purified splenic Ly-6C+ macrophages from drug-treated mice. However, the transfer of Ly-6C+ macrophages from drug-treated mice failed to block ongoing diabetes in wild-type NOD mice. These data demonstrate that the modified gene expression and functional alteration of T lymphocytes and macrophages collectively contribute to diabetes protection afforded by the histone modifier in female NOD mice.

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Section: Discussionmentioning

confidence: 97%

Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection

Jayaraman

Arianas

Jayaraman

2021

Preprint

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“…Mice NOD/ShiLtJ (NOD), NOD.129S7(B6)-Rag1 tm1Mom /J (NOD.Rag1 À/À ), and NOD.B6-Ptprc b /6908MrkTacJ (NOD.Cd45.2) mice were procured from The Jackson Laboratory and maintained at the Medical College of Wisconsin. NOD.Tnfrsf9 À/À and NOD.Il27ra À/À mice have been previously described (26,33).…”

Section: Methodsmentioning

confidence: 99%

“…We previously demonstrated that IL-27 signaling in CD8 T cells promotes T1D progression in NOD mice (26). Direct IL-27 signaling enhanced the accumulation of islet-infiltrating CD8 T cells and promoted their expression of T-bet and IFNg (26).…”

Section: Differential Gene Regulatory Network Activity In Islet-infil...mentioning

confidence: 99%

“…IL-27, a heterodimeric cytokine composed of two noncovalently linked subunits, EBV-induced gene 3 and IL-27p28, has been shown to play a role in the differentiation of CD8 T cells (2125). We previously demonstrated that IL-27 signaling was required for the development of T1D in the NOD mouse and that direct IL-27 signaling enhanced the diabetogenic activity of CD8 T cells (26). Although direct IL-27 signaling did not have a significant effect on the phenotype of CD8 T cells in the spleen and PLNs, it promoted their accumulation and expression of T-bet and IFNg in the pancreatic islets (26).…”

mentioning

confidence: 98%

“…We previously demonstrated that IL-27 signaling was required for the development of T1D in the NOD mouse and that direct IL-27 signaling enhanced the diabetogenic activity of CD8 T cells (26). Although direct IL-27 signaling did not have a significant effect on the phenotype of CD8 T cells in the spleen and PLNs, it promoted their accumulation and expression of T-bet and IFNg in the pancreatic islets (26). This is consistent with the previous observation that there is further differentiation of CD8 T cells within the local islet environment (9,10).…”

mentioning

confidence: 99%

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Self-Renewing Islet TCF1+ CD8 T Cells Undergo IL-27–Controlled Differentiation to Become TCF1− Terminal Effectors during the Progression of Type 1 Diabetes

Ciecko

Schauder

Foda

et al. 2021

The Journal of Immunology

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Author contributions: A.E.C. and D.M.S. designed experiments, performed experimental work, analyzed results, prepared figures, and wrote the manuscript. B.F. performed experimental work and provided intellectual contribution. G.P. provided critical cell sorting expertise. M.Y.K. analyzed single-cell RNA sequencing (scRNA-seq) data and revised the manuscript. C.-W.L. analyzed the scRNA-seq data. R.B. generated gene regulatory network models. W.R.D. provided reagents and intellectual contribution. W.C. and Y.-G.C. conceived the study, supervised the project, and revised the manuscript.The scRNA-seq data presented in this article have been submitted to the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE155595) under accession number GSE155595.

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Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example

Lichti

Wan

2023

Seminars in Immunology

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Interleukin-27 is essential for type 1 diabetes development and Sjögren syndrome-like inflammation

Cited by 4 publications

References 0 publications

Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection

Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection

Self-Renewing Islet TCF1+ CD8 T Cells Undergo IL-27–Controlled Differentiation to Become TCF1− Terminal Effectors during the Progression of Type 1 Diabetes

Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example

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