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Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets
- Source :
- Journal of Clinical Investigation. 121:3024-3028
- Publication Year :
- 2011
- Publisher :
- American Society for Clinical Investigation, 2011.
-
Abstract
- Type 1 diabetes is characterized by destruction of insulin-producing β cells in the pancreatic islets by effector T cells. Tregs, defined by the markers CD4 and FoxP3, regulate immune responses by suppressing effector T cells and are recruited to sites of action by the chemokine CCL22. Here, we demonstrate that production of CCL22 in islets after intrapancreatic duct injection of double-stranded adeno-associated virus encoding CCL22 recruits endogenous Tregs to the islets and confers long-term protection from autoimmune diabetes in NOD mice. In addition, adenoviral expression of CCL22 in syngeneic islet transplants in diabetic NOD recipients prevented β cell destruction by autoreactive T cells and thereby delayed recurrence of diabetes. CCL22 expression increased the frequency of Tregs, produced higher levels of TGF-β in the CD4+ T cell population near islets, and decreased the frequency of circulating autoreactive CD8+ T cells and CD8+ IFN-γ–producing T cells. The protective effect of CCL22 was abrogated by depletion of Tregs with a CD25-specific antibody. Our results indicate that islet expression of CCL22 recruits Tregs and attenuates autoimmune destruction of β cells. CCL22-mediated recruitment of Tregs to islets may be a novel therapeutic strategy for type 1 diabetes.
- Subjects :
- CD4-Positive T-Lymphocytes
T cell
Autoimmunity
Mice, SCID
Nod
Biology
medicine.disease_cause
T-Lymphocytes, Regulatory
Autoimmune Diseases
Islets of Langerhans
Mice
Immune system
Mice, Inbred NOD
medicine
Animals
NOD mice
Chemokine CCL22
Brief Report
Pancreatic islets
Interleukin-2 Receptor alpha Subunit
FOXP3
Forkhead Transcription Factors
General Medicine
Rats
Diabetes Mellitus, Type 1
medicine.anatomical_structure
Immunology
CD8
Subjects
Details
- ISSN :
- 00219738
- Volume :
- 121
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....654aff26fab56fa9f70cb0274078ddd1