Involvement of gut immune system in systemic autoimmune diseases and peripheral tolerance has been reported. However, details of cell migration from gut to systemic immune system remains unclear. Here, we investigated migration of B cells, and effector CD4+ T cells including Th1, Th17, and Treg cells from gut.
To track gut-originated cells, we used photoconvertible protein KikGR/hCD2Fxp3 mice. Majority of Peyer’s patches (PPs) or 80% of small intestine lamina propria (SI-LP) was exposed to violet light to mark cells by photoconversion of KikGR from green to Red. Then, 24 hours later, PPs-derived or SI-LP-derived KikGR-Red cells in the mesenteric lymph node (MLN), cutaneous lymph nodes (CLNs), and spleen were analyzed. Th1 and Th17 cells were detected by intracellular staining of IFN-γand IL-17. Treg cells were gated by hCD2 expression.
PPs-derived KikGR-Red cells in B cells (11.2%) and T cells (2.5%) in MLN were higher than those in spleen (B cells; 4.6%, T cells; 1.4%) and CLNs (B cells; 3.6%, T cells; 1.3%), suggesting that PPs-derived lymphocyte migrate to CLNs and spleen via MLN as similar to SI-LP-derived lymphocytes. In KikGR-Red phenotype in MLN, PPs-derived (11.2%) and SI-LP-derived (0.67%) B cells, and PPs-derived (2.2%) and SI-LP-derived (0.22%) Tregs were detected, suggesting that majority of gut-derived B cells and Tregs were PPs-derived. On the other hand, PPs-derived and SI-LP-derived KikGR-Red Th1 cells were detected at similar frequencies in MLNs (1.4% vs. 1.0%) and spleen (0.25% vs. 0.17%). In addition, similar frequencies of PPs-derived and SI-LP-derived KikGR-Red Th17 cells were detected in MLNs and spleen (1.4% - 2.3%), and CLNs (0.21% vs. 0.32%). These results suggested that SI-LP as well as PPs is important tissue for supplying Th1 and Th17 cells to systemic immune system in the steady state.