The membrane-bound chemokine CXCL16 expressed on follicle-associated epithelium and M cells mediates lympho-epithelial interaction in GALT.
The recently identified CXCL16 has dual functions as a transmembrane adhesion molecule and a soluble chemokine. In this study we found that CXCL16 mRNA and protein were expressed constitutively on the follicle-associated epithelium covering Peyer's patches (PPs), isolated lymphoid follicles, and cecal patches, but minimally on the villous epithelium in the murine gastrointestinal tract. The CXCL16 receptor CXCR6/Bonzo was constitutively expressed on subpopulations of CD4+ and CD8+ T cells isolated from PPs. The expression of CXCR6/Bonzo on the PP T cells was up-regulated after stimulation with anti-CD3 and anti-CD28 mAbs. The activated PP T cells showed chemotactic migration in response to the soluble N-terminal chemokine domain of CXCL16. Furthermore, the activated PP T cells selectively adhered to cells expressing murine CXCL16. To determine the physiological role of CXCL16 in GALT, we first carefully analyzed T cell distribution in PPs. T cells localized not only in the interfollicular region but also at a lesser frequency in the subepithelial dome (SED) and in the germinal center of lymphoid follicles. Consistently, the majority of the adoptive transferred activated T cells migrated into the SED and the interfollicular region. However, the neutralization of CXCL16 specifically reduced the migration of the adoptive, transferred, activated T cells into the SED of PPs. These data suggest that CXCL16 expressed on the follicle-associated epithelium plays an important role in the recruitment and retention of activated T cells in the SED and should, at least partially, be responsible for lymphocyte compartmentalization in GALT.
Hase
Koji
K
Research Center for Allergy and Immunology, RIKEN, Yokohama, Kanagawa, Japan.
Murakami
Takaya
T
Takatsu
Hiroyuki
H
Shimaoka
Takeshi
T
Iimura
Mitsutoshi
M
Hamura
Kimiyo
K
Kawano
Kazuya
K
Ohshima
Sayaka
S
Chihara
Risa
R
Itoh
Kikuji
K
Yonehara
Shin
S
Ohno
Hiroshi
H
D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D018925:Chemokines / Q000276:immunology; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051116:Receptors, Scavenger / Q000096:biosynthesis* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D018925:Chemokines; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; D012333:RNA, Messenger; D051116:Receptors, Scavenger