Gadd45beta is important for perpetuating cognate and inflammatory signals in T cells

Abstract

Gadd45beta (growth arrest and DNA damage-inducible, beta) is involved in cell cycle arrest, apoptosis, signal transduction and cell survival. In T cells, Gadd45b was rapidly induced by T cell receptor (TCR) and inflammatory signals. Deficiency of Gadd45beta in CD4+ T cells impaired their responses to TCR stimulation or inflammatory cytokines. ERK, p38 and JNK activation were all substantially suppressed in Gadd45beta-deficient CD4+ T cells. Cytokine production by Gadd45beta-deficient CD4+ T cells was also impaired. Furthermore, Gadd45beta mediated inflammatory cytokine production by dendritic cells, and Gadd45beta-deficient mice showed an impaired T helper type 1 response during Listeria monocytogenes infection. Gadd45beta is therefore a critical feedback regulator that perpetuates both cognate and inflammatory signals.