Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation

TY - JOUR

T1 - Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation

AU - Fu, Hongmei

AU - Kishore, Madhav

AU - Gittens, Beartice

AU - Wang, Guosu

AU - Coe, David

AU - Komarowska, Izabela

AU - Infante, Elvira

AU - Ridley, Anne J.

AU - Cooper, Dianne

AU - Perretti, Mauro

AU - Marelli-Berg, Federica M.

PY - 2014/3/14

Y1 - 2014/3/14

N2 - Localization of CD4+CD25+Foxp3+ regulatory T (Treg) cells to lymphoid and non-lymphoid tissue is instrumental for the effective control of immune responses. Compared with conventional T cells, Treg cells constitute a minute fraction of the T-cell repertoire. Despite this numeric disadvantage, Tregs efficiently migrate to sites of immune responses reaching an optimal number for the regulation of T effector (Teff) cells. The array and levels of adhesion and chemokine receptor expression by Tregs do not explain their powerful migratory capacity. Here we show that recognition of self-antigens expressed by endothelial cells in target tissue is instrumental for efficient Treg recruitment in vivo. This event relies upon IFN-γ-mediated induction of MHC-class-II molecule expression by the endothelium and requires optimal PI3K p110δ activation by the T-cell receptor. We also show that, once in the tissue, Tregs inhibit Teff recruitment, further enabling a Teff:Treg ratio optimal for regulation.

AB - Localization of CD4+CD25+Foxp3+ regulatory T (Treg) cells to lymphoid and non-lymphoid tissue is instrumental for the effective control of immune responses. Compared with conventional T cells, Treg cells constitute a minute fraction of the T-cell repertoire. Despite this numeric disadvantage, Tregs efficiently migrate to sites of immune responses reaching an optimal number for the regulation of T effector (Teff) cells. The array and levels of adhesion and chemokine receptor expression by Tregs do not explain their powerful migratory capacity. Here we show that recognition of self-antigens expressed by endothelial cells in target tissue is instrumental for efficient Treg recruitment in vivo. This event relies upon IFN-γ-mediated induction of MHC-class-II molecule expression by the endothelium and requires optimal PI3K p110δ activation by the T-cell receptor. We also show that, once in the tissue, Tregs inhibit Teff recruitment, further enabling a Teff:Treg ratio optimal for regulation.

U2 - 10.1038/ncomms4436

DO - 10.1038/ncomms4436

M3 - Article

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 3436

ER -