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Thymic stromal lymphopoetin is critical for recovery from DSS induced colitis
Author(s) -
Reardon Colin,
Lechman Matthias,
Mak Tak W
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb421
Subject(s) - colitis , thymic stromal lymphopoietin , immunology , inflammation , immune system , cytokine , medicine
Thymic stromal lymphopoetin (TSLP) influences a plethora of immune functions; including in the colonic mucosa. Aims Here we assessed the role of TSLP in mediating recovery from colonic inflammation. Methods Controls (WT), mice deficient for TSLP (TSLP −/− ), or bone marrow (BM) chimeric mice using TSLP receptor deficient (TSLPR −/− ) BM were subjected to dextran sodium sulfate colitis (DSS; 5% w/v). Mice were assessed daily for weight loss, and inflammation assessed 8 days post‐DSS during overt disease. Results TSLP −/− mice do not display enhanced colonic inflammation during DSS‐induced colitis as determined by similar weight loss, T H 1/T H 17 cytokine production and histological damage compared to WT controls. Despite this, TSLP −/− mice failed to recover from colitis, with progressive weight loss resulting in death. Reduced collagen deposition and increased neutrophil elastase (NE) activity but not metallomatrix protease activity occurred in TSLP −/− as compared to WT mice. Increased NE activity was paralleled by a reduction in the endogenous inhibitor of this enzyme, secretory leukocyte peptidase inhibitor (SLPI). Critically, BM chimeras identified that TSLPR on non‐hematopoeitc cells were sufficient for recovery from DSS‐induced colitis. Additionally, we identified TSLPR on intestinal epithelial cells (IEC), and stimulation of this receptor induced the expression of SLPI. Conclusion TSLP‐elicited signaling through TSLPR on IEC is a critical mediator in wound healing that does not involve restraining of T H 1/T H 17 cytokines. The disparity between TSLP −/− and TSLPR −/− mice suggests that signaling downstream of TSLPR could occur in response to cytokines other than TSLP.