| First Author | Lindsay RS | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 10 | PubMed ID | 34415994 |
| Mgi Jnum | J:323411 | Mgi Id | MGI:7261126 |
| Doi | 10.1084/jem.20200464 | Citation | Lindsay RS, et al. (2021) MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites. J Exp Med 218(10):e20200464 |
| abstractText | 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. |
