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

Research output: Contribution to journalArticlepeer-review

99 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 languageEnglish (US)
Pages (from-to)160-170
Number of pages11
JournalImmunity
Volume39
Issue number1
DOIs
StatePublished - Jul 25 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response'. Together they form a unique fingerprint.

Cite this