Understanding mechanisms of immune regulation is key to developing immunotherapies for autoimmunity and cancer. We examined the role of mononuclear phagocytes during peripheral T cell regulation in type 1 diabetes and melanoma. MERTK expression and activity in mononuclear phagocytes in the pancreatic islets promoted islet T cell regulation, resulting in reduced sensitivity of T cell scanning for cognate antigen in prediabetic islets. MERTK-dependent regulation led to reduced T cell activation and effector function at the disease site in islets and prevented rapid progression of type 1 diabetes. In human islets, MERTK-expressing cells were increased in remaining insulin-containing islets of type 1 diabetic patients, suggesting that MERTK protects islets from autoimmune destruction. MERTK also regulated T cell arrest in melanoma tumors. These data indicate that MERTK signaling in mononuclear phagocytes drives T cell regulation at inflammatory disease sites in peripheral tissues through a mechanism that reduces the sensitivity of scanning for antigen leading to reduced responsiveness to antigen.
MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites
Disclosures: The authors declare no competing interests exist.
- Award Id(s): 5-SRA-2018-557-Q-R
- Award Id(s): 2018PG-T1D053
- Award Id(s): 2-2012-197
- Award Id(s): 1R01DK111733-01
- Award Id(s): P30-DK116073
- Award Id(s): T32: 5T32AI007405-27
- Award Id(s): AWD-112499
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Robin S. Lindsay, Jennifer C. Whitesell, Kristen E. Dew, Erika Rodriguez, Adam M. Sandor, Dayna Tracy, Seth F. Yannacone, Brittany N. Basta, Jordan Jacobelli, Rachel S. Friedman; MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites. J Exp Med 4 October 2021; 218 (10): e20200464. doi: https://doi.org/10.1084/jem.20200464
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