CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid tissue-inducer cells, and formation of isolated lymphoid follicles

The chemokine CXCL13 is overexpressed in the intestine during inflammation. To mimic this condition, we created transgenic mice-expressing CXCL13 in intestinal epithelial cells. CXCL13 expression promoted a marked increase in the number of B cells in the lamina propria and an increase in the size and number of lymphoid follicles in the small intestine. Surprisingly, these changes were associated with a marked increase in the numbers of ROR gamma t(+)NKp46(-)CD3(-)CD4(+) and ROR gamma t(+)NKp46(+) cells. The ROR gamma t(+)NKp46(-)CD3(-)CD4(+) cells expressed CXCR5, the receptor for CXCL13, and other markers of lymphoid tissue-inducer cells, such as LT alpha, LT beta, and TNF-related activation-induced cytokine (TRANCE). ROR gamma t(+)NKp46(-)CD3(-)CD4(+) gut LTi cells produced IL-22, a cytokine implicated in epithelial repair; and expressed the IL-23 receptor, a key regulator of IL-22 production. These results suggest that overexpression of CXCL13 in the intestine during inflammatory conditions favors mobilization of B cells and of LTi and NK cells with immunomodulatory and reparative functions.