Mononuclear phagocytes drive Mertk-dependent T cell regulation at autoimmune and tumor sites

Lindsay, R. S.; Dew, K. E.; Rodriguez, E.; Whitesell, J. C.; Tracy, D.; Sandor, A. M.; Yannacone, S. F.; Jacobelli, J.; Friedman, R. S.

doi:10.1101/687061

bioRxiv · 10.1101/687061

Mononuclear phagocytes drive Mertk-dependent T cell regulation at autoimmune and tumor sites

Lindsay, R. S.·Dew, K. E.·Rodriguez, E.·Whitesell, J. C.·Tracy, D.·Sandor, A. M.·Yannacone, S. F.·Jacobelli, J.·Friedman, R. S.

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Abstract

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 pre-diabetic islets. MERTK-dependent regulation led to reduced T cell activation and effector function at the disease site in the 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 the 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.

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Lindsay, R. S., Dew, K. E., Rodriguez, E., Whitesell, J. C., Tracy, D., Sandor, A. M., Yannacone, S. F., Jacobelli, J., Friedman, R. S.. 2019-06-29. Mononuclear phagocytes drive Mertk-dependent T cell regulation at autoimmune and tumor sites. https://doi.org/10.1101/687061

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