TY - JOUR
T1 - T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response
AU - CarreraSilva, Eugenio A.
AU - Chan, Pamela Y.
AU - Joannas, Leonel
AU - Errasti, Andrea E.
AU - Gagliani, Nicola
AU - Bosurgi, Lidia
AU - Jabbour, Maurice
AU - Perry, Anthony
AU - Smith-Chakmakova, Faye
AU - Mucida, Daniel
AU - Cheroutre, Hilde
AU - Burstyn-Cohen, Tal
AU - Leighton, Jonathan A.
AU - Lemke, Greg
AU - Ghosh, Sourav
AU - Rothlin, Carla V.
N1 - Funding Information:
We thank R. Medzhitov for critical reading of this manuscript. We also thank S. Huber, A. Iwasaki, P. Kavathas, P. Lincona-Limón, S. Nish, D. Schenten and E. Zuniga for helpful suggestions and discussions. This research was supported by grants from the National Institutes of Health (R01 AI077058 to G.L., R01 AI089824 to C.V.R. and S.G., CA95060 to S.G., and T32 AI007019 to P.Y.C), by the Crohn’s and Colitis Foundation (to C.V.R and S.G.), by the American Heart Association (C.V.R), American Asthma Foundation (C.V.R.), Lupus Research Institute (C.V.R), CONICET Postdoctoral Fellowship (A.E.E.), and a Gershon-Trudeau Postdoctoral Fellowship (E.A.C.S.).
PY - 2013/7/25
Y1 - 2013/7/25
N2 - 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 overreactiveimmune responses. Tcells, 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 Tcells led to increased expression of costimulatory molecules and cytokines in DCs and enhanced immune responses to Tcell-dependent antigens, as well as increased colitis. Additionally, PROS1 was expressed in activated human Tcells, 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.
AB - 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 overreactiveimmune responses. Tcells, 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 Tcells led to increased expression of costimulatory molecules and cytokines in DCs and enhanced immune responses to Tcell-dependent antigens, as well as increased colitis. Additionally, PROS1 was expressed in activated human Tcells, 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.
UR - http://www.scopus.com/inward/record.url?scp=84880730041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880730041&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2013.06.010
DO - 10.1016/j.immuni.2013.06.010
M3 - Article
C2 - 23850380
AN - SCOPUS:84880730041
SN - 1074-7613
VL - 39
SP - 160
EP - 170
JO - Immunity
JF - Immunity
IS - 1
ER -