TOB1 Blocks Intestinal Mucosal Inflammation Through Inducing ID2-Mediated Suppression of Th1/Th17 Cell Immune Responses in IBD

• DOI: 10.1016/j.jcmgh.2021.12.007
• Publication Date: 2021-12-14T17:32:13Z
• Authors: Ritian Lin; Caiyun Ma; Leilei Fang; Chunjin Xu; Cui Zhang; Xiaohan Wu; Wei Wu; Ruixin Zhu; Yingzi Cong; Zhanju Liu
• Keywords: CD4+ T Cells; TOB1; RC799-869; Lymphocyte Activation; Mice; 03 medical and health sciences; Mucosal Inflammation; Animals; Humans; Intestinal Mucosa; RNA, Small Interfering; Original Research; Inhibitor of Differentiation Protein 2; Homeodomain Proteins; Inflammation; 0303 health sciences; Tumor Suppressor Proteins; Inflammatory Bowel Disease; Intracellular Signaling Peptides and Proteins; ID2; Diseases of the digestive system. Gastroenterology; Th1 Cells; Colitis; Inflammatory Bowel Diseases; 3. Good health; Th17 Cells; Sulfonic Acids

TOB1 is an anti-proliferative protein of Tob/BTG family and typically involved in the tumorigenesis T cell activation. Although associated with helper 17 cell-related autoimmunity, its role modulating cell-mediated immune responses IBD remains poorly understood. Here, we explored expression underlying mechanisms pathogenesis inflammatory bowel disease (IBD).TOB1 ID2 patients was examined by quantitative real time polymerase chain reaction immunohistochemistry. CD4+ cells were transfected lentivirus expressing TOB1, ID2, short hairpin RNA RNA, respectively, Tob1-/-CD4+ Id2. Experimental colitis established Tob1-/- mice trinitrobenzene sulfonic acid enema Rag1-/- reconstituted Tob1-/-CD45RBhighCD4+ to further explore Tob1 intestinal mucosal inflammation. Splenic sorted determine transcriptome differences sequencing.TOB1 decreased inflamed mucosa peripheral blood compared healthy subjects. Overexpression downregulated differentiate into Th1/Th17 control Severe observed through or cells, animals. sequencing analysis revealed as functional target inhibit differentiation cells. Mechanistically, Smad4/5 induce restrain differentiation.TOB1 restrains inflammation suppressing via Smad4/5-ID2 pathway. It may serve a novel therapeutic for treatment human IBD.