Single-cell Transcriptomic Analysis Reveals Rich Pituitary-immune Interactions under Systemic Inflammation. Mus musculus

The pituitary represents an essential hub in the hypothalamus-pituitary-adrenal (HPA) axis. Pituitary hormone-producing cells (HPCs) release several hormones to regulate fundamental bodily functions under normal and stress conditions. It is well established that the pituitary endocrine gland modulates the immune system by releasing adrenocorticotropic hormone (ACTH) in response to neuronal activation in the hypothalamus. However, it remains unclear how systemic inflammation regulates the transcriptomic profiles of pituitary HPCs. Here, we performed single-cell RNA- sequencing (scRNA-seq) of the pituitary and revealed that upon inflammation, all major pituitary HPCs respond robustly in a cell type-specific manner, with corticotropes displaying the strongest reaction. Systemic inflammation also led to the production and release of noncanonical bioactive molecules, including NPTX2 by corticotropes, to modulate immune homeostasis. Meanwhile, HPCs upregulate the gene expression of chemokines that facilitate the communication between the HPCs and immune cells. Together, our study reveals extensive interactions between the pituitary and immune system, suggesting the roles of the pituitary in mediating the effects of inflammation on many aspects of body physiology.