IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation

Abstract

cytokines ͉ inflammasome ͉ Th1 ͉ Th17 ͉ Th2

T-cell–intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy

“…First, it has been widely reported that IL-1 signaling is required for T H 2-mediated immunity and allergy (36)(37)(38)(39). More specifically, IL-1 signaling is required to activate T H 2 cells directly in vivo (13,40). Second, a relationship between IL-1R/ubiquitin C and Trim24 has been suggested previously (15-19); however, the requirement of Trim24 for IL-1R expression has not been reported.…”

“…In line with this prediction, IL-1R signaling is required for T H 2-dependent immunity (36,37) and T H 2-mediated airway allergy (38,39), supporting observations presented here with Trim24 −/− T cells. Specifically, IL-1 signaling is required to activate T H 2 cells in vivo (13,40), and, as we show here, IL-1R signaling in T cells can exacerbate T H 2-driven airway allergy. In support of this upstream mechanistic link, Tim24 −/− T H 2 cells were refractory to IL-1β-induced activation/proliferation and cytokine production in vitro, and mice with Tim24 −/− T cells failed to develop exacerbated disease when activated with allergen and IL-1β.…”

“…IL-1R signaling is essential for the effector phase of T H 2-mediated airway allergy (38,39), and IL-1 can directly activate T H 2 cells in vivo (13,40). However, it is unclear how this process is regulated and whether Trim24 is required for IL-1-mediated T H 2 cell activation in vivo.…”

“…Tertiary cytokine signals by tissue-associated inflammatory cytokines, including members of the IL-1 family (12,13), and the "alarmins" (IL-25 and TSLP) (14) have been proposed to activate T H 2 cells; however, the regulation and pathways involved are unclear. An IL-1R (IL-1 receptor)/ubiquitin C/Trim24 (tripartite motif-containing 24) axis has been identified previously (15)(16)(17)(18)(19), but the involvement of Trim24 in T H 2 biology has not been reported.…”

A ativação do receptor NOD2 contribui para a imunopatogenia do diabetes tipo 1 experimental

“…Em síntese, a IL-1β e a IL-18 agem em linfócitos de diferentes formas como através da expressão do receptor para IL-2R e assim, prolongando a sobrevivência destas células, assim como aumentando a proliferação e diferenciação de linfócitos B (BEN-SASSON et al, 2009;MALISZEWSKI et al, 1990). Em adição, a IL-1β e a IL-18 atuam no desvio e amplificação da resposta Th17 e Th1, respectivamente (CHUNG et al, 2009;GUO et al, 2009;HATA et al, 2004).…”