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Series GSE130979 Query DataSets for GSE130979
Status Public on Sep 23, 2019
Title CCL21 Expression in Beta Cells Induces Antigen-Expressing Stromal Cell Networks in the Pancreas and Prevents Autoimmune Diabetes in Mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Tumors induce tolerance towards their antigens by producing the chemokine CCL21, leading to the formation of tertiary lymphoid organs (TLOs). Ins2-CCL21 transgenic, non-obese diabetic (NOD) mice express CCL21 in pancreatic β-cells and do not develop autoimmune diabetes. We investigated by which mechanisms CCL21 expression prevented diabetes. Islet infiltrates of 4 week-old Ins2-CCL21 mice were enriched in naïve CD4+ T cells and compartmentalized within networks of CD45- gp38+ CD31- fibroblastic reticular cell (FRC)-like stromal cells. Importantly, 12 week-old Ins2-CCL21 NOD islets contained FRC-like cells with enhanced expression of β-cell autoantigens and gene expression profiles consistent with regulatory, anti-inflammatory properties and increased contractility. Consistently, transgenic mice harbored fewer autoreactive T cells and higher proportion of Tregs in the islets. Using adoptive transfer and islet transplantation models, we demonstrate that the formation of TLOs in Ins2-CCL21 transgenic islets is critical for regulation of autoimmunity and while the effect is systemic, the induction may be mediated locally by lymphocyte trafficking through TLOs. Overall, our findings suggest that CCL21 promotes TLOs that differ from inflammatory TLOs associated with islets in T1D in that they resemble lymph nodes, contain FRC-like cells expressing β-cell autoantigens and are able to induce systemic and antigen-specific tolerance leading to diabetes prevention. These findings suggest that CCL21 may be exploited for novel immunoregulation approaches to treat autoimmune diabetes.
Overall design Examination of lymph node derived Fibroblastic Reticular Cells (FRCs), FRC-like cells from pancreatic islets and islet infiltrating leukocytes in both Ins2-CCL21 transegnic NOD (TG+ samples) and non-transgenic NOD (TG- samples) mice
Contributor(s) Gonzalez Badillo F, Zisi Tegou F, Griswold AJ, Tomei A
Citation(s) 31371518
Submission date May 09, 2019
Last update date Sep 25, 2019
Contact name Anthony Griswold
Organization name University of Miami
Street address 1501 NW 10th Ave, BRB 318
City Miami
State/province FL
ZIP/Postal code 33136
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (27)
GSM3758171 islet_CD45_TG-_1
GSM3758172 islet_CD45_TG-_2
GSM3758173 islet_CD45_TG-_3
BioProject PRJNA542161
SRA SRP197377

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Supplementary file Size Download File type/resource
GSE130979_RAW.tar 8.4 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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