IFN- γ and IL-17A regulate intestinal crypt production of CXCL10 in the healthy and inflamed colon.

IFN-γ and IL-17A regulate intestinal crypt production of CXCL10 in the healthy and inflamed colon. Am J Physiol Gastrointest Liver Physiol. 2019 Dec 02;: Authors: Walrath T, Malizia RA, Zhu X, Sharp SP, DSouza SS, Lopez-Soler R, Parr B, Kartchner B, Lee EC, Stain SC, Iwakura Y, OConnor W Abstract During intestinal inflammation, immature cells within the intestinal crypt are called upon to replenish lost epithelial cell populations, promote tissue regeneration and restore barrier integrity. Inflammatory mediators including TH1/TH17-associated cytokines influence tissue health and regenerative processes, yet how these cytokines directly influence the colon crypt epithelium, and whether the crypt remains responsive to these cytokines during active damage and repair, remains unclear. Here, using laser-capture microdissection and primary colon spheroid culture we show that the cytokine milieu regulates the ability of the colonic crypt epithelium to participate in pro-inflammatory signaling. IFN-γ induces the TH1-recruiting, pro-inflammatory chemokine CXCL10/IP10 in primary murine intestinal crypt epithelium. CXCL10 was also induced in colonic spheroids derived from mice with active, experimentally-induced colitis, suggesting that the crypt can actively secrete CXCL10 in select cytokine environments during colitis. Colon expression of cxcl10 further increased during infectious and non-infectious colitis in Il17a-/- mice, demonstrating th...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research