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| Status |
Public on Jan 30, 2023 |
| Title |
Heterogeneity of islet-infiltrating interleukin-21+ CD4 T cells in a mouse model of type 1 diabetes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Interleukin (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 disease progression. However, little is known about their phenotype and differentiation states. To fill this gap, we generated 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 antigens. Single-cell RNA sequencing revealed that most 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, less differentiated early effectors, 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 continuously produce IL-21 throughout their differentiation process, highlighting the important sources of IL-21 in T1D pathogenesis.
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| Overall design |
Islet-infiltrating CD4 T cells from NOD.Il21V/+ mice were isolated by fluorescence-activated cell sorting (FACS) according to the presence of absence of Venus signal and analyzed by scRNA-seq.
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| Contributor(s) |
Ciecko AE, Wang Y, Harleston S, Drewek A, Serreze DV, Geurts AM, Lin C, Chen Y |
| Citation(s) |
36762954 |
| Submission date |
Aug 25, 2022 |
| Last update date |
May 02, 2023 |
| Contact name |
Yi-Guang Chen |
| E-mail(s) |
yichen@mcw.edu
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| Organization name |
Medical College of Wisconsin
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| Department |
Pediatrics
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| Street address |
9200 W. Wisconsin Ave.
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| City |
Milwaukee |
| State/province |
WI |
| ZIP/Postal code |
53226 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA873273 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212009_RAW.tar |
25.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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