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.