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 RORγt + NKp46 -CD3 -CD4 + and RORγt +NKp46 + cells. The RORγt +NKp46 -CD3 -CD4 + cells expressed CXCR5, the receptor for CXCL13, and other markers of lymphoid tissue-inducer cells, such as LTα, LTβ, and TNF-related activation-induced cytokine (TRANCE). RORγt + 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.
CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid tissue-inducer cells, and formation of isolated lymphoid follicles / F. Marchesi, A. Martin, N. Thirunarayanan, E. Devany, L. Mayer, M. Grisotto, G. Furtado, S. Lira. - In: MUCOSAL IMMUNOLOGY. - ISSN 1933-0219. - 2:6(2009), pp. 486-494.
CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid tissue-inducer cells, and formation of isolated lymphoid follicles
F. MarchesiPrimo
;
2009
Abstract
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 RORγt + NKp46 -CD3 -CD4 + and RORγt +NKp46 + cells. The RORγt +NKp46 -CD3 -CD4 + cells expressed CXCR5, the receptor for CXCL13, and other markers of lymphoid tissue-inducer cells, such as LTα, LTβ, and TNF-related activation-induced cytokine (TRANCE). RORγt + 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.Pubblicazioni consigliate
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