TFF2 deficiency exacerbates weight loss and alters immune cell and cytokine profiles in DSS colitis, and this cannot be rescued by wild-type bone marrow

Judd, L, Chalinor, H, Walduck, A, Pavlic, D, Däbritz, J, Dubeykovskaya, Z, Wang, T, Menheniott, T and Giraud, A 2015, 'TFF2 deficiency exacerbates weight loss and alters immune cell and cytokine profiles in DSS colitis, and this cannot be rescued by wild-type bone marrow', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 308, no. 1, pp. G12-G24.


Document type: Journal Article
Collection: Journal Articles

Title TFF2 deficiency exacerbates weight loss and alters immune cell and cytokine profiles in DSS colitis, and this cannot be rescued by wild-type bone marrow
Author(s) Judd, L
Chalinor, H
Walduck, A
Pavlic, D
Däbritz, J
Dubeykovskaya, Z
Wang, T
Menheniott, T
Giraud, A
Year 2015
Journal name American Journal of Physiology - Gastrointestinal and Liver Physiology
Volume number 308
Issue number 1
Start page G12
End page G24
Total pages 13
Publisher American Physiological Society
Abstract The trefoil factor TFF2 is a member of a tripartite family of small proteins that is produced by the stomach and the colon. Recombinant TFF2, when applied intrarectally in a rodent model of hapten colitis, hastens mucosal healing and reduces inflammatory indexes. Additionally, TFF2 is expressed in immune organs, supporting a potential immunomodulatory and reparative role in the bowel. In this study we confirm that TFF2 is expressed in the colon and is specifically enriched in epithelial cells relative to colonic leukocytes. TFF2-deficient, but not TFF1-deficient, mice exhibit a more severe response to acute or chronic dextran sulfate (DSS)-induced colitis that correlates with a 50% loss of expression of TFF3, the principal colonic trefoil. In addition, the response to acute colitis is associated with altered expression of IL-6 and IL-33, but not other inflammatory cytokines. While TFF2 can reduce macrophage responsiveness and block inflammatory cell recruitment to the colon, the major role in limiting the susceptibility to acute colitis appears to be maintenance of barrier function. Bone marrow transfer experiments demonstrate that leukocyte expression of TFF2 is not sufficient for prevention of colitis induction but, rather, that the gastrointestinal epithelium is the primary source of TFF2. Together, these findings illustrate that epithelial TFF2 is an important endogenous regulator of gut mucosal homeostasis that can modulate immune and epithelial compartments. Because of its extreme stability, even in the corrosive gut lumen, TFF2 is an attractive candidate as an oral therapeutic scaffold for future drug development in the treatment of inflammatory bowel disease.
Subject Infectious Agents
Keyword(s) Mucosal immunity
Trefoil
Trefoil factor 2
IL-33
Colitis
Dextran sodium sulfate
DOI - identifier 10.1152/ajpgi.00172.2014
Copyright notice Copyright © 2015 the American Physiological Society
ISSN 0193-1857
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