T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response

• Autores: Carrera Silva, Eugenio Antonio; Chan, Pamela Y.; Joannas, Leonel; Errasti, Andrea Emilse; Gagliani, Nicola; Bosurgi, Lidia; Jabbour, Maurice; Perry, Anthony; Smith Chakmakova, Faye; Mucida, Daniel; Cheroutre, Hilde; Burstyn Cohen, Tal; Leighton, Jonathan A.; Lemke, Greg; Ghosh, Sourav; Rothlin, Carla V.
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: T Cells; Pros1; Dendritic Cell Activation
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Dendritic cell (DC) activation is essential for the induction of immune defense against pathogens, yet needs to be tightly controlled to avoid chronic inflammation and exaggerated immune responses. Here, we identify a mechanism of immune homeostasis by which adaptive immunity, once triggered, tempers DC activation and prevents overreactive immune responses. T cells, once activated, produced Protein S (Pros1) that signaled through TAM receptor tyrosine kinases in DCs to limit the magnitude of DC activation. Genetic ablation of Pros1 in mouse T cells led to increased expression of costimulatory molecules and cytokines in DCs and enhanced immune responses to T cell-dependent antigens, as well as increased colitis. Additionally, PROS1 was expressed in activated human T cells, and its ability to regulate DC activation was conserved. Our results identify a heretofore unrecognized, homeostatic negative feedback mechanism at the interface of adaptive and innate immunity that maintains the physiological magnitude of the immune response.
Fil: Carrera Silva, Eugenio Antonio. University of Yale. School of Medicine; Estados Unidos de América; Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina;
Fil: Chan, Pamela Y.. University of Yale. School of Medicine; Estados Unidos de América;
Fil: Joannas, Leonel. University of Yale. School of Medicine; Estados Unidos de América;
Fil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina; University of Yale. School of Medicine; Estados Unidos de América; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;
Fil: Gagliani, Nicola. University of Yale. School of Medicine; Estados Unidos de América;
Fil: Bosurgi, Lidia. University of Yale. School of Medicine; Estados Unidos de América;
Fil: Jabbour, Maurice. University Of Arizona; Estados Unidos de América;
Fil: Perry, Anthony. Banner MD Anderson Cancer Center; Estados Unidos de América;
Fil: Smith Chakmakova, Faye. Saint Joseph’s Hospital and Medical Center; Estados Unidos de América;
Fil: Mucida, Daniel. La Jolla Institute for Allergy and Immunology; Estados Unidos de América;
Fil: Cheroutre, Hilde. La Jolla Institute for Allergy and Immunology; Estados Unidos de América;
Fil: Burstyn Cohen, Tal. Salk Institute for Biological Studies; Estados Unidos de América;
Fil: Leighton, Jonathan A.. Mayo Clinic Arizona; Estados Unidos de América;
Fil: Lemke, Greg. Salk Institute for Biological Studies; Estados Unidos de América;
Fil: Ghosh, Sourav. University Of Arizona; Estados Unidos de América;
Fil: Rothlin, Carla V.. University of Yale. School of Medicine; Estados Unidos de América;