title: Enhanced differentiation of intraepithelial lymphocytes in the intestine of polymeric immunoglobulin receptor-deficient mice.
abstract: To clarify the effect of secretory IgA (sIgA) deficiency on gut homeostasis, we examined intraepithelial lymphocytes (IELs) in the small intestine (SI) of polymeric immunoglobulin receptor-deficient (pIgR(-/-) ) mice. The pIgR(-/-) mice exhibited the accumulation of CD8αβ(+) T-cell receptor (TCR)-αβ(+) IELs (CD8αβ(+) αβ-IELs) after weaning, but no increase of CD8αβ(+) γδ-IELs was detected in pIgR(-/-) TCR-β(-/-) mice compared with pIgR(+/+) TCR-β(-/-) mice. When 5-bromo-2'-deoxyuridine (BrdU) was given for 14 days, the proportion of BrdU-labelled cells in SI-IELs was not different between pIgR(+/+) mice and pIgR(-/-) mice. However, the proportion of BrdU-labelled CD8αβ(+) -IELs became higher in pIgR(-/-) mice than pIgR(+/+) mice 10 days after discontinuing BrdU-labelling. Intravenously transferred splenic T cells migrated into the intraepithelial compartments of pIgR(+/+) TCR-β(-/-) mice and pIgR(-/-) TCR-β(-/-) mice to a similar extent. In contrast, in the case of injection of immature bone marrow cells, CD8αβ(+) αβ-IELs increased much more in the SI of pIgR(-/-) TCR-β(-/-) mice than pIgR(+/+) TCR-β(-/-) mice 8 weeks after the transfer. αβ-IELs from pIgR(-/-) mice could produce more interferon-γ and interleukin-17 than those of pIgR(+/+) mice, and intestinal permeability tended to increase in the SI of pIgR(-/-) mice with aging. Taken together, these results indicate that activated CD8αβ(+) αβ-IELs preferentially accumulate in pIgR(-/-) mice through the enhanced differentiation of immature haematopoietic precursor cells, which may subsequently result in the disruption of epithelial integrity.
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kato-Nagaoka
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamakawa
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsujibe
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Naito
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Setoyama
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Shida
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nanno
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D001973:Bromodeoxyuridine; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D007071:Immunoglobulin A, Secretory / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics*; D013194:Staining and Labeling
chemical_list: D007071:Immunoglobulin A, Secretory; D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019056:Receptors, Polymeric Immunoglobulin; D007371:Interferon-gamma; D001973:Bromodeoxyuridine
keywords: bone marrow cell; intestinal permeability; intraepithelial lymphocyte; polymeric immunoglobulin receptor; spleen cell