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

Eugenio A. CarreraSilva; Pamela Y. Chan; Leonel Joannas; Andrea E. Errasti; Nicola Gagliani; Lidia Bosurgi; Maurice Jabbour; Anthony Perry; Faye Smith-Chakmakova; Daniel Mucida; Hilde Cheroutre; Tal Burstyn-Cohen; Jonathan A. Leighton; Greg Lemke; Sourav Ghosh; Carla V. Rothlin

doi:10.1016/j.immuni.2013.06.010

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

Eugenio A. CarreraSilva, Pamela Y. Chan, Leonel Joannas, Andrea E. Errasti, Nicola Gagliani, Lidia Bosurgi, Maurice Jabbour, Anthony Perry, Faye Smith-Chakmakova, Daniel Mucida, Hilde Cheroutre, Tal Burstyn-Cohen, Jonathan A. Leighton, Greg Lemke, Sourav Ghosh^*, Carla V. Rothlin

^*Corresponding author for this work

Institute of Biomedical Research at the Faculty of Dental Medicine

Research output: Contribution to journal › Article › peer-review

144 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	160-170
Number of pages	11
Journal	Immunity
Volume	39
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2013.06.010
State	Published - 25 Jul 2013

Bibliographical note

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.).

Access to Document

10.1016/j.immuni.2013.06.010

Cite this

CarreraSilva, E. A., Chan, P. Y., Joannas, L., Errasti, A. E., Gagliani, N., Bosurgi, L., Jabbour, M., Perry, A., Smith-Chakmakova, F., Mucida, D., Cheroutre, H., Burstyn-Cohen, T., Leighton, J. A., Lemke, G., Ghosh, S., & Rothlin, C. V. (2013). T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response. Immunity, 39(1), 160-170. https://doi.org/10.1016/j.immuni.2013.06.010

@article{d788f01180b74cac9a4946f059c6278a,

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

abstract = "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.",

author = "CarreraSilva, {Eugenio A.} and Chan, {Pamela Y.} and Leonel Joannas and Errasti, {Andrea E.} and Nicola Gagliani and Lidia Bosurgi and Maurice Jabbour and Anthony Perry and Faye Smith-Chakmakova and Daniel Mucida and Hilde Cheroutre and Tal Burstyn-Cohen and Leighton, {Jonathan A.} and Greg Lemke and Sourav Ghosh and Rothlin, {Carla V.}",

note = "Funding Information: We thank R. Medzhitov for critical reading of this manuscript. We also thank S. Huber, A. Iwasaki, P. Kavathas, P. Lincona-Lim{\'o}n, 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{\textquoteright}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.). ",

year = "2013",

month = jul,

day = "25",

doi = "10.1016/j.immuni.2013.06.010",

language = "אנגלית",

volume = "39",

pages = "160--170",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "1",

}

CarreraSilva, EA, Chan, PY, Joannas, L, Errasti, AE, 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 2013, 'T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response', Immunity, vol. 39, no. 1, pp. 160-170. https://doi.org/10.1016/j.immuni.2013.06.010

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

U2 - 10.1016/j.immuni.2013.06.010

DO - 10.1016/j.immuni.2013.06.010

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 23850380

AN - SCOPUS:84880730041

SN - 1074-7613

VL - 39

SP - 160

EP - 170

JO - Immunity

JF - Immunity

IS - 1

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this