A new study published in the journal Brain, Behavior, and Immunity indicates that the stress hormone epinephrine (also known as adrenaline) is able to drive a Th2/Th17-shift in dendritic cells (DCs) in the presence of a pathogenic stimulus.
Dendritic cells cytokine and chemokine profiles are able to shape CD4+ T cell pathways and phenotypes and thus affect several T cell-related inﬂammatory conditions. DC-associated IL-12 and IL-23 cytokine production has a key role in dictating DC ability to instruct CD4+ T cell phenotypes.
IL-12 promotes the differentiation of Th1 effector cells, whereas IL-23 is known to induce the production of antimicrobial peptides via IL-22 and maintain the Th17 cell subset, which is an important mediator of adaptive immune responses as well as regulator of innate responses, including neutrophil recruitment.
In the Brain, Behavior, and Immunity study, Byung-Jin Kim and Harlan Jones address the effect of adrenal medullary stress hormone epinephrine on DCs behavior.
They demonstrate that exposing murine bone marrow-derived dendritic cells (BMDC) to epinephrine then bacterial lipopolysaccharide (LPS) induces a preferential reduction in IL-12p40 mRNA transcripts, but an increase of IL-23p19 and IL-12p35 mRNA expression, associated with a decrease of IL-12p70 and a concomitant increase in IL-23 and IL-10 cytokine production.
IL-10, a key facilitator of Th2 and regulatory CD4+T cells responses is found prevalent in many chronic inﬂammatory disease states. These changes correspond with increased IL-4 and IL-17A, but not IFN-gamma cytokine production by CD4+ T cells.
According to the authors, these results suggest that exposure to stress-derived epinephrine dictates dendritic cells to generate a dominant Th2/Th17 phenotype in the context of subsequent exposure to a pathogenic stimulus. Thus, the adrenergic stimulation can affect inﬂammatory conditions by favoring Th17 differentiation through augmentation of DC cytokine functioning.