RESUMO
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.
Assuntos
Autoimunidade/fisiologia , Ilhotas Pancreáticas/enzimologia , Fagócitos/fisiologia , Linfócitos T/imunologia , c-Mer Tirosina Quinase/imunologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos/imunologia , Antígenos/metabolismo , Antígenos CD11/metabolismo , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Humanos , Ilhotas Pancreáticas/imunologia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Neoplasias Experimentais/enzimologia , Neoplasias Experimentais/imunologia , Fagócitos/imunologia , Piperazinas/farmacologia , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismoRESUMO
BACKGROUND: Craniofacial injuries secondary to earthquake-related trauma are uncommonly reported and can pose a significant reconstructive challenge. The objective of this study is to report and analyze earthquake-related craniofacial injury reconstruction and the disaster relief capabilities of a U.S. Navy hospital ship. METHODS: A review of earthquake-related injuries treated over 40 days requiring craniofacial reconstruction onboard a U.S. Navy hospital ship was performed. RESULTS: From January 20 to February 28, 2010 (40 days), 869 patients were admitted to the USNS Comfort. Thirty-three patients (4 percent) treated by the craniofacial service underwent 93 craniofacial surgical procedures. Average patient hospitalization time was 17 days (range, 5 to 38 days). The fractures treated included nine mandibles, 12 zygomaticomaxillary-orbital complexes, 16 orbital floors, eight Le Fort, four naso-orbitoethmoid, and two cranial vault fractures. The soft-tissue injuries treated were two heminasal avulsions, two traumatic cleft lips, and eight other complex facial lacerations. Short-term complications included wound dehiscence (6 percent) and postoperative malocclusion (6 percent). There were no postsurgical wound infections, visual field changes, or mortality. CONCLUSIONS: Complex craniofacial surgery services can be safely delivered onboard a United States Navy hospital ship for devastating injuries caused by natural disasters. Although craniofacial injuries represented a small percentage of the total patients admitted to our hospital ship, the survivors of facial injury required complex and multiple procedures to achieve optimal results. Despite heavy wound contamination and the intrinsic delay in presentation associated with mass casualty triage, facial fractures can be treated adequately and with low morbidity and mortality.