Enhanced differentiation of intraepithelial lymphocytes in the intestine of polymeric immunoglobulin receptor‐deficient mice

Abstract

Summary 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.

Enhanced survival following oral and systemic Salmonella enterica serovar Typhimurium infection in polymeric immunoglobulin receptor knockout mice

“…The increase in the stool IgG of the pIgR KO mice may also be serving as a protective compensatory mechanism to prevent bacterial translocation. Kato-Nagaoka et al recently confirmed earlier reports of increased bacterial counts from the mLNs of pIgR KO mice, however they detected lower values than previous studies [ 13 , 28 , 31 ]. Several factors, including technical details of the assay and variability in local animal facility microbiomes may account for these differences.…”

The Role of the Polymeric Immunoglobulin Receptor and Secretory Immunoglobulins during Mucosal Infection and Immunity

“…Despite differences in microbial communities, colonic mucus thickness is similar in pIgR KO mice compare to controls [ 14 ]. Small intestinal mucus thickness has not been directly assessed; however, small intestinal permeability may increase with age in pIgR KO mice compared to controls [ 59 ]. 6.…”

The Preventative Effect of Dietary <i>Apostichopus japonicus</i> on Intestinal Microflora Dysregulation in Immunosuppressive Mice Induced by Cyclophosphamide

“…Lysozyme and secretory IgA (SIgA), which is composed of two IgA molecules and is transported by pIgR, are two important mucosal immune system effectors. They help prevent infection and remove antigens crossing the mucosal barrier [4] [5]. Our previous study had indicated that cyclophosphamide could induce the expression of lysozyme and sIgA [6].…”