Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation.
Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5's influence on inflammatory bowel diseases (IBDs), we investigated TRAF5 deficiency's effect on dextran sulfate sodium- (DSS-) induced colitis. Colitis was induced in TRAF5 knockout (KO) mice and their wild-type (WT) littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4(+) T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4(+) T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Jian
J
Shang
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Lixia
L
Li
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Xiaobing
X
Wang
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Huaqin
H
Pan
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Shi
S
Liu
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Ruohang
R
He
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Jin
J
Li
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China.
Qiu
Q
Zhao
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003092:Colitis; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D048015:TNF Receptor-Associated Factor 5 / Q000235:genetics / Q000378:metabolism*
D020381:Interleukin-17; D012333:RNA, Messenger; D048015:TNF Receptor-Associated Factor 5; D016264:Dextran Sulfate; D009195:Peroxidase