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- Title
WNT5A transforms intestinal CD8αα⁺ IELs into an unconventional phenotype with pro-inflammatory features.
- Authors
Zhao, Di; Xu, Antao; Dai, Zhanghan; Peng, Jiangchen; Zhu, Mingming; Shen, Jun; Zheng, Qing; Ran, Zhihua
- Abstract
<bold>Background: </bold>Intestinal intraepithelial lymphocytes that reside within the epithelium of the intestine form one of the main branches of the immune system. A majority of IELs express CD8α homodimer together with other molecules associated with immune regulation. Growing evidence points to the WNT signaling pathway as a pivotal piece in the immune balance and focuses on its direct regulation in intestinal epithelium. Therefore we decided to investigate its role in IELs' immune status determination.<bold>Method: </bold>DSS colitis was induced in male C57BL mice. IELs were isolated from colon samples using mechanical dissociation followed by percoll gradient purification and Magnetic-activated cell sorting. Phenotype and cytokine production and condition with Wnts were analyzed by flow cytometry, real-time PCR or ELISA. Proliferation of lymphocytes were evaluated using CFSE dilution. Cell responses after WNT pathway interference were also evaluated.<bold>Results: </bold>Non-canonical WNT pathway elements represented by FZD5, WNT5A and NFATc1 were remarkably elevated in colitis IELs. The non-canonical WNT5A skewed them into a pro-inflammatory category as measured by inhibitory cell surface marker LAG3, LY49E, NKG2A and activated marker CD69 and FASL. Gaining of a pro-inflammatory marker was correlated with increased IFN-γ production but not TNF whilst decreased TGF-β and IL-10. Both interrupting WNT5A/PKC pathway and adding canonical WNT stimulants could curtail its immune-activating effect.<bold>Conclusion: </bold>Canonical and non-canonical WNT signals act in opposing manners concerning determining CD8αα(+) IELs immune status. Targeting non-canonical WNT pathway may be promising in tackling inflammatory bowel disease.
- Subjects
ANIMALS; BIOLOGICAL models; CELL lines; CELLULAR signal transduction; CYTOKINES; INTESTINAL mucosa; MICE; T cells; ULCERATIVE colitis
- Publication
BMC Gastroenterology, 2015, Vol 15, Issue 1, p173
- ISSN
1471-230X
- Publication type
journal article
- DOI
10.1186/s12876-015-0402-3