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.
|Titolo:||CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid tissue-inducer cells, and formation of isolated lymphoid follicles|
MARCHESI, FEDERICA (Primo)
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2009|
|Digital Object Identifier (DOI):||10.1038/mi.2009.113|
|Appare nelle tipologie:||01 - Articolo su periodico|