This study reveals the presence of dendritic cells (DCs) in the pituitary gland, which play a role in communicating immune activation to the hypothalamic pituitary adrenal (HPA) axis. Using enhanced yellow fluorescent protein (eyfp) expression as a reporter for CD11c, a marker of DCs, we demonstrate anatomically the presence of CD11c/eyfp+ cells throughout the pituitary. Flow cytometric analysis shows that the predominant cellular phenotype of pituitary CD11c/eyfp+ cells resembles that of non-lymphoid DCs. In vivo and in vitro immune challenge with lipopolysaccharide (LPS) stimulates these pituitary CD11c/eyfp+ DCs, but not eyfp(neg) cells, to increase levels of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α. In vivo analysis of plasma glucocorticoid (GC) and adrenocorticotropic hormone (ACTH) levels at this early phase of the immune response to LPS suggest that pro-inflammatory cytokine production by DCs within the pituitary may activate the release of GCs from the adrenals via ACTH. Pituitary CD11c/eyfp+ cells also express annexin A1 (ANXA1), indicating a role in GC signal attenuation. In summary, our data demonstrate that a resident DC population of the pituitary gland coordinates GC release in the early phase of systemic immune activation, thereby providing an essential immune signaling sentinel for the initial shaping of the systemic immune response to LPS.
