| First Author | Liu R | Year | 2019 |
| Journal | Life Sci Alliance | Volume | 2 |
| Issue | 2 | PubMed ID | 30948494 |
| Mgi Jnum | J:287472 | Mgi Id | MGI:6391742 |
| Doi | 10.26508/lsa.201900296 | Citation | Liu R, et al. (2019) Constitutive STAT5 activation regulates Paneth and Paneth-like cells to control Clostridium difficile colitis. Life Sci Alliance 2(2) |
| abstractText | Clostridium difficile impairs Paneth cells, driving intestinal inflammation that exaggerates colitis. Besides secreting bactericidal products to restrain C. difficile, Paneth cells act as guardians that constitute a niche for intestinal epithelial stem cell (IESC) regeneration. However, how IESCs are sustained to specify Paneth-like cells as their niche remains unclear. Cytokine-JAK-STATs are required for IESC regeneration. We investigated how constitutive STAT5 activation (Ca-pYSTAT5) restricts IESC differentiation towards niche cells to restrain C. difficile infection. We generated inducible transgenic mice and organoids to determine the effects of Ca-pYSTAT5-induced IESC lineages on C. difficile colitis. We found that STAT5 absence reduced Paneth cells and predisposed mice to C. difficile ileocolitis. In contrast, Ca-pYSTAT5 enhanced Paneth cell lineage tracing and restricted Lgr5 IESC differentiation towards pYSTAT5(+)Lgr5(-)CD24(+)Lyso(+) or cKit(+) niche cells, which imprinted Lgr5(hi)Ki67(+) IESCs. Mechanistically, pYSTAT5 activated Wnt/beta-catenin signaling to determine Paneth cell fate. In conclusion, Ca-pYSTAT5 gradients control niche differentiation. Lack of pYSTAT5 reduces the niche cells to sustain IESC regeneration and induces C. difficile ileocolitis. STAT5 may be a transcription factor that regulates Paneth cells to maintain niche regeneration. |
