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- Title
T helper type 17 pathway suppression by appendicitis and appendectomy protects against colitis.
- Authors
Cheluvappa, R.; Luo, A. S.; Grimm, M. C.
- Abstract
Appendicitis followed by appendectomy ( AA) at a young age protects against inflammatory bowel disease ( IBD). We wanted to characterize the role of the T helper type 17 (Th17) system involved in this protective effect. AA was performed on 5-week-old male BALB/c mice and distal-colon samples were harvested. Mice with two laparotomies each served as sham-sham ( SS) controls. RNA was extracted from four individual colonic samples per group ( AA and SS groups) and each sample microarray-analysed and reverse transcription-polymerase chain reaction ( RT- PCR)-validated. Gene-set enrichment analysis ( GSEA) showed that the Th17 recruitment factor gene CCL20 was significantly suppressed at both 3 days post- AA and 28 days post- AA. Although Th17 cell development differentiation factor genes TGF-β2 and TGF-β3 were significantly up-regulated 3 days post- AA, GSEA 28 days post- AA showed that AA down-regulated 29 gene-sets associated with TGF-β1, TGF-β2 and TGF-β3 in contrast to none up-regulated with any of these genes. GSEA showed substantial down-regulation of gene-sets associated with Th17 lymphocyte recruitment, differentiation, activation and cytokine expression in the AA group 28 days post- AA. We conclude that Th17-system cytokines are kept under control by AA via down-regulation of proinflammatory CCL20, a rapid down-regulation of pro- Th17 cell differentiation genes TGF-β2 and TGF-β3, suppression of RORC-associated gene-sets, increased protective STAT1 expression and suppression of 81 'pro- Th17' system gene-sets. AA suppresses the Th17 pathway leading to colitis amelioration. Further characterization of Th17-associated genes and biological pathways will assist in the development of better therapeutic approaches in IBD management.
- Subjects
T helper cells; APPENDICITIS; APPENDECTOMY; COLITIS prevention; INFLAMMATORY bowel diseases; REVERSE transcriptase polymerase chain reaction; CELL differentiation; PREVENTION
- Publication
Clinical & Experimental Immunology, 2014, Vol 175, Issue 2, p316
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/cei.12237