ArticleJournal of immunology (Baltimore, Md. : 1950)2023
Heterogeneity of Islet-Infiltrating IL-21+ CD4 T Cells in a Mouse Model of Type 1 Diabetes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Both soluble and cell surface CD137 expressed by Foxp3+ CD4 T cells restrain autoimmune diabetes.The Journal of experimental medicine · 2026Article
- Aberrant IL-21/STAT3 signaling disrupts regulatory T cell function and CD4Frontiers in immunology · 2026Article
- Lymphocyte activation gene 3 in autoimmune disease: from molecular mechanisms to clinical applications.Frontiers in immunology · 2026Review
- Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus.Cell reports · 2025Article
- Article
- An interleukin-27-centered cytokine circuit regulates macrophage and T cell interactions in autoimmune diabetes.iScience · 2025Article
- Polyfunctional T follicular helper cells drive checkpoint-inhibitor diabetes and are targeted by JAK inhibitor therapy.JCI insight · 2025Article
- IL-27 promotes pathogenic T cells in a mouse model of Sjögren's disease.Clinical immunology (Orlando, Fla.) · 2024Article
- A pathologically expanded, clonal lineage of IL-21-producing CD4+ T cells drives inflammatory neuropathy.The Journal of clinical investigation · 2024Article
- A pathologically expanded, clonal lineage of IL-21 producing CD4+ T cells drives Inflammatory neuropathy.bioRxiv : the preprint server for biology · 2024Article
- Deletion of Vβ3Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
IL-21 is essential for type 1 diabetes (T1D) development in the NOD mouse model. IL-21-expressing CD4 T cells are present in pancreatic islets where they contribute to T1D progression. However, little is known about their phenotype and differentiation states. To fill this gap, we generated, to our knowledge, a novel IL-21 reporter NOD strain to further characterize IL-21+ CD4 T cells in T1D. IL-21+ CD4 T cells accumulate in pancreatic islets and recognize β cell Ags. Single-cell RNA sequencing revealed that CD4 T effector cells in islets actively express IL-21 and they are highly diabetogenic despite expressing multiple inhibitory molecules, including PD-1 and LAG3. Islet IL-21+ CD4 T cells segregate into four phenotypically and transcriptionally distinct differentiation states, that is, less differentiated early effectors, T follicular helper (Tfh)-like cells, and two Th1 subsets. Trajectory analysis predicts that early effectors differentiate into both Tfh-like and terminal Th1 cells. We further demonstrated that intrinsic IL-27 signaling controls the differentiation of islet IL-21+ CD4 T cells, contributing to their helper function. Collectively, our study reveals the heterogeneity of islet-infiltrating IL-21+ CD4 T cells and indicates that both Tfh-like and Th1 subsets produce IL-21 throughout their differentiation process, highlighting the important sources of IL-21 in T1D pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.