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 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.
Marchesi
F
F
Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
Martin
A P
AP
Thirunarayanan
N
N
Devany
E
E
Mayer
L
L
Grisotto
M G
MG
Furtado
G C
GC
Lira
S A
SA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D054382:Chemokine CXCL13 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018928:Immunity, Mucosal / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000276:immunology*; D000097043:Interleukin-22
D054382:Chemokine CXCL13; D007378:Interleukins; D000097043:Interleukin-22; C486386:Cxcl13 protein, mouse