Gut bacteria induce IgA expression in pituitary hormone-secreting cells during aging

Pituitary hormone decline is a hallmark of aging. However, the precise gene regulation mechanism during pituitary aging is unclear. Here, we characterized the cell population alteration and global transcriptional change during pituitary aging through single-cell RNA sequencing (scRNA-seq). We found that mRNA-encoding components of protein translational machinery declined the most in the pituitary during aging. Remarkably, Immunoglobulin A (IgA) was found to be expressed in hormone-secreting cells, and the IgA expression level increased dramatically in aged pituitary. Moreover, the pituitary IgA expression was regulated by gut microbiota. The non-hematopoietic origin of the IgA+ cells in the pituitary was further confirmed through bone marrow transplantation. Somatotropes were identified as the most prominent IgA-producing cells through lineage tracing. Thus, pituitary hormone-secreting cells can generate IgA in an age-dependent manner, and such a process is influenced by gut bacteria.