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.