T cell-derived protein S engages TAM receptor signaling in dendritic cells to control the magnitude of the immune response.

CARRERA SILVA EA; CHAN PY; LEONEL JOANNAS; ERRASTI ANDREA E; GAGLIANI N; BOSURGI L; JABBOUR M; PERRY A; SMITH-CHAKMAKOVA F; MUCIDA D; CHEROUTRE H; BURSTYN-COHEN T; LEIGHTON JA; LEMKE G; GHOSH S; ROTHLIN CV

IMMUNITY

CELL PRESS

Lugar: United States; Año: 2013 vol. 39 p. 160 - 170

1074-7613

Dendritic cell (DC) activation is essential for the induction of immune defenseagainst pathogens, yet needs to be tightly controlled to avoid chronicinflammation and exaggerated immune responses. Here, we identify a mechanism ofimmune homeostasis by which adaptive immunity, once triggered, tempers DCactivation and prevents overreactive immune responses. T cells, once activated,produced Protein S (Pros1) that signaled through TAM receptor tyrosine kinases inDCs to limit the magnitude of DC activation. Genetic ablation of Pros1 in mouseT cells led to increased expression of costimulatory molecules and cytokines inDCs and enhanced immune responses to T cell-dependent antigens, as well asincreased colitis. Additionally, PROS1 was expressed in activated human T cells, and its ability to regulate DC activation was conserved. Our results identify aheretofore unrecognized, homeostatic negative feedback mechanism at the interfaceof adaptive and innate immunity that maintains the physiological magnitude of theimmune response.