title: TRAF3 regulates the effector function of regulatory T cells and humoral immune responses.
abstract: 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.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Chang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.forename: Nahum
authors.initials: N
authors.lastname: Puebla-Osorio
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Brian E
authors.initials: BE
authors.lastname: Gilbert
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Ullrich
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D002849:Chromatography, Gas; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000096:biosynthesis; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D015345:Oligonucleotide Probes / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D048008:TNF Receptor-Associated Factor 3 / Q000276:immunology / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D015345:Oligonucleotide Probes; D048008:TNF Receptor-Associated Factor 3