Spatial heterogeneity for APRIL production by eosinophils in the small intestine

The study demonstrates that microbiotal component(s) from the ileum and colon induce(s) APRIL expression in bloodborne eosinophils to mediate plasma-cell survival in the lamina propria. This APRIL-dependent survival pathway is not active in the duodenum. Eosinophils may reside in the lower intestine to play several homeostatic functions. Regulation of IgA(+) plasma-cell (PC) homeostasis is one of these functions. Here, we assessed regulation of expression for a proliferation-inducing ligand (APRIL), a key factor from the TNF superfamily for PC homeostasis, in eosinophils from the lower intestine. We observed a strong heterogeneity, since duodenum eosinophils did not produce APRIL at all, whereas a large majority of eosinophils from the ileum and right colon produced it. This was evidenced both in the human and mouse adult systems. At these places, the human data showed that eosinophils were the only cellular sources of APRIL. The number of IgA(+) PCs did not vary along the lower intestine, but ileum and right colon IgA(+) PC steady-state numbers significantly diminished in APRIL-deficient mice. Use of blood cells from healthy donors demonstrated that APRIL expression in eosinophils is inducible by bacterial products. Use of germ-free and antibiotics-treated mice confirmed the dependency on bacteria for APRIL production by eosinophils from the lower intestine. Taken together, our study shows that APRIL expression by eosinophils is spatially regulated in the lower intestine with a consequence on the APRIL dependency for IgA(+) PC homeostasis.