TRAF3 regulates the effector function of regulatory T cells and humoral immune responses
Regulatory T cells (Treg cells) control different aspects of immune responses, but how the effector functions of Treg cells are regulated is incompletely understood. Here we identified TNF receptor-associated factor 3 (TRAF3) as a regulator of Treg cell function. Treg cell-specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by an increase in the Th1 type of effector/memory T cells. Moreover, the ablation of TRAF3 in Treg cells resulted in increased antigen-stimulated activation of follicular T helper cells (TFH cells), coupled with heightened formation of germinal centers and production of high-affinity IgG antibodies. Although the loss of TRAF3 did not reduce the overall frequency of Treg cells, it attenuated the antigen-stimulated production of follicular Treg cells (TFR cells). TRAF3 signaling in Treg cells was required to maintain high level expression of inducible co-stimulator (ICOS), which in turn was required for TFR cell generation and inhibition of antibody responses. These findings establish TRAF3 as a mediator of Treg cell function in the regulation of antibody responses and suggest a role for TRAF3 in mediating ICOS expression in Treg cells.
|Authors||Chang, J. H.; Hu, H.; Jin, J.; Puebla-Osorio, N.; Xiao, Y.; Gilbert, B. E.; Brink, R.; Ullrich, S. E.; Sun, S. C.:|
|Publisher Name||JOURNAL OF EXPERIMENTAL MEDICINE|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/24378539|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/11880|