Systemic autoimmune abnormalities alter the morphology of mucosa-associated lymphoid tissues in the rectum of MRL/MpJ-Faslpr/lpr mice.

Abstract

Systemic autoimmune diseases (ADs) might affect the morphology and function of gut-associated lymphoid tissue (LTs) indirectly; however, their exact relationship remains unclear. Therefore, we investigated mouse LTs in the anorectal canal and morphologically compared them between MRL/MpJ-Fas^+/+ and MRL/MpJ-Fas^lpr/lpr mice. LT aggregations, also known as rectal mucosa-associated lymphoid tissues (RMALTs), were exclusively seen in the lamina propria and submucosa of the rectum. The mean size and number of the LT aggregations both significantly increased in MRL/MpJ-Fas^lpr/lpr mice compared to those in MRL/MpJ-Fas^+/+ mice. The distance from the anorectal junction to the first LT aggregate was significantly shorter in MRL/MpJ-Fas^lpr/lpr mice than that in MRL/MpJ-Fas^+/+ mice. Immunostaining revealed that the RMALTs included CD3⁺, CD4⁺, and CD8⁺ T cells; B220⁺ B cells; IBA1⁺ macrophages; Ki67⁺ proliferative cells; and PNAd⁺ high-endothelial venules (HEVs). The numbers of macrophages, proliferative cells, CD4⁺ T cells, CD8⁺ T cells, and HEVs were significantly increased in MRL/MpJ-Fas^lpr/lpr mice compared to those in MRL/MpJ mice. Furthermore, the gene expression levels of chemokines (Cxcl9 and Cxcl13) and their corresponding receptors (Cxcr3 and Cxcr5) were significantly higher in MRL/MpJ-Fas^lpr/lpr mice than those in MRL/MpJ-Fas^+/+ mice. Although the morphology of rectal epithelium was comparable between the strains, M cell number was significantly higher in MRL/MpJ-Fas^lpr/lpr mice than in MRL/MpJ-Fas^+/+ mice. Thus, ADs could alter RMALT morphology, and quantitative changes in T-cell subsets, proliferative cells, macrophages, HEVs, chemokine expression, and M cells could affect their cell composition and development.