08 August 2016 : Animal Research
Elevated IL-23R Expression and Foxp3+Rorγt+ Cells in Intestinal Mucosa During Acute and Chronic ColitisJiayin YangB, Lili XuACDEFG
Med Sci Monit 2016; 22:2785-2792
BACKGROUND: IL-23/IL-23R signaling plays a pivotal role during the course of inflammatory bowel diseases (IBD). However, the underlying mechanisms are poorly characterized. Foxp3+ regulatory T cells are critical in the maintenance of gut immune homeostasis and therefore are important in preventing the development of IBD. This study was performed to clarify the association between IL-23/IL-23R signaling and Foxp3+ regulatory T cells in colitis.
MATERIAL AND METHODS: Acute and chronic mouse colitis models were established by administering mice DSS in drinking water. IL-23R, IL-23, IL-I7, and IFN-γ expression level, as well as regulatory T cell, Th17-, and Th1-related transcription factors Foxp3, RORgt, and T-bet were assayed by real-time PCR. The frequency of Foxp3+ RORγt+ cells in a Foxp3+ cell population in colon mucosa during acute and chronic colitis was evaluated through flow cytometry. The signaling pathway mediated by IL-23R in the colon mucosa from acute colitis mice and chronic colitis mice was monitored by Western blot analysis.
RESULTS: We detected elevated IL-23R, IL-23, and IFN-γ expression in colon mucosa during acute and chronic colitis and found increased IL-17 in acute colitis mice. Transcription factors Foxp3 and T-bet were elevated in colon mucosa during acute and chronic colitis. Phosphorylation of Stat3 was greatly enhanced, indicating the activation of IL-23R function in colitis mice. The percentage of Foxp3+ T cells in acute and chronic colitis mice was comparable to control mice, but there was a 2-fold increase of Foxp3+ RORγt+ cells among the Foxp3+ cell population in acute and chronic colitis mice compared to control mice.
CONCLUSIONS: These findings indicate that the induction of Foxp3+ RORgt+ T cells could be enhanced during inflammation in the intestine where IL-23R expression is greatly induced. Our study highlights the importance of IL-23R expression level and the instability of Foxp3+ regulatory T cells in the development of inflammatory bowel diseases.
Keywords: Colitis - metabolism, CD4-Positive T-Lymphocytes - immunology, Animals, Cytokines - metabolism, Disease Models, Animal, Forkhead Transcription Factors - metabolism, Interferon-gamma - metabolism, Interleukin-17 - metabolism, Interleukin-23 - metabolism, Intestinal Mucosa - metabolism, Mice, Mice, Inbred C57BL, Receptors, Interleukin - genetics, Signal Transduction, T-Lymphocytes, Regulatory - metabolism
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