Tonic TCR and IL-1-beta signaling mediate phenotypic alterations of naive CD4+ T cells
Description
Inert naive CD4+ T (TN) cells differentiate into functional helper T or regulatory T (Treg) cell subsets upon encountering antigens, enabling properly-directed immune responses. Although all TN cells can differentiate into any Th and Treg cell subsets, recent studies have revealed some heterogeneity among TN cells. Here, by developing novel reporter mice that detect ongoing T cell receptor (TCR) signaling, we revealed the effects of tonic TCR signaling on TN cells, while unexpectedly finding that IL-1-beta affects TN cell characteristics. IL-1-beta signals to TN cells particularly in the spleen and in inflamed tissues, attenuating their differentiation potential to Treg cells. A mouse colitis model revealed reversible effects of IL-1-beta on TN cells' colitogenic activities. Aberrant regulation of IL-1-betatargets in TN cells was detected in colitis patients, showing its association with therapeutic response to anti-TNF therapies. Our work revealed the IL-1-beta-TN cell axis as a novel regulator of immune response.