The Th1 life cycle: molecular control of IFN-gamma to IL-10 switching

TY - JOUR

T1 - The Th1 life cycle: molecular control of IFN-gamma to IL-10 switching

AU - Cope, Andrew

AU - Le Friec, Gaelle

AU - Cardone, John

AU - Kemper, Claudia

PY - 2011/6

Y1 - 2011/6

N2 - Control of IFN-gamma-secreting T helper (Th) 1 cells prevents autoimmunity and immunopathology during infection. IL-10-mediated suppression of Th1 cells is achieved not only through IL-10 produced extrinsically, but also through a negative feedback loop that induces "intrinsic" IL-10 expression in cells also expressing IFN-gamma, during Th1 lineage differentiation. Targeting this Th1 cell IFN-gamma to IL-10 switching is a tantalising prospect for developing therapeutics for Th1-mediated diseases. In this review, the molecular pathways that regulate IFN-gamma versus IL-10 expression in Th1 cells are examined, with focus on the role of complement regulator and T cell costimulatory molecule CD46, and also discussed are challenges and controversies in the field.

AB - Control of IFN-gamma-secreting T helper (Th) 1 cells prevents autoimmunity and immunopathology during infection. IL-10-mediated suppression of Th1 cells is achieved not only through IL-10 produced extrinsically, but also through a negative feedback loop that induces "intrinsic" IL-10 expression in cells also expressing IFN-gamma, during Th1 lineage differentiation. Targeting this Th1 cell IFN-gamma to IL-10 switching is a tantalising prospect for developing therapeutics for Th1-mediated diseases. In this review, the molecular pathways that regulate IFN-gamma versus IL-10 expression in Th1 cells are examined, with focus on the role of complement regulator and T cell costimulatory molecule CD46, and also discussed are challenges and controversies in the field.

U2 - 10.1016/j.it.2011.03.010

DO - 10.1016/j.it.2011.03.010

M3 - Literature review

VL - 32

SP - 278

EP - 286

JO - TRENDS IN IMMUNOLOGY

JF - TRENDS IN IMMUNOLOGY

IS - 6

ER -