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

Mucosal Immunol. 2009 Nov;2(6):486-94. doi: 10.1038/mi.2009.113. Epub 2009 Sep 9.

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 RORgammat(+)NKp46(-)CD3(-)CD4(+) and RORgammat(+)NKp46(+) cells. The RORgammat(+)NKp46(-)CD3(-)CD4(+) cells expressed CXCR5, the receptor for CXCL13, and other markers of lymphoid tissue-inducer cells, such as LTalpha, LTbeta, and TNF-related activation-induced cytokine (TRANCE). RORgammat(+)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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Chemokine CXCL13 / biosynthesis
  • Chemokine CXCL13 / genetics
  • Chemokine CXCL13 / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunity, Mucosal / immunology
  • Immunohistochemistry
  • Inflammation / immunology
  • Interleukin-22
  • Interleukins / biosynthesis
  • Interleukins / immunology*
  • Intestinal Mucosa / immunology*
  • Killer Cells, Natural / immunology*
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • Stem Cells / immunology*

Substances

  • Chemokine CXCL13
  • Cxcl13 protein, mouse
  • Interleukins