Figure 1. Circuits of the neuro-immune axis.

The autonomic nervous system connects peripheral immune organs with the central nervous system and regulates homeostatic and inflammatory functions. A) Sympathetic nerves innervate Nestin⁺ bone marrow niche cells. Circadian release of NE activates β₃ adrenergic receptors (b₃AR) on perivascular Nestin⁺ niche cells, which leads to rhythmic downregulation of CXCL12 and the subsequent release of hematopoietic stem cells (HSC) into the blood stream during the resting period. B) The inflammatory reflex: nerve endings of the vagus nerve sense inflammatory mediators and transport the signals to the brain stem. From there, the signal travels via efferent cholinergic vagal nerves to the celiac ganglion and through adrenergic fibers of the splenic nerve and delivers NE to β₂ adrenergic receptors (b₂AR) on a subset of splenic T cells, which in turn secrete acetylcholine (ACh) that binds to α7 nicotinic acetylcholine receptors (a₇nAChR) on marginal zone macrophages and suppresses the production of inflammatory cytokines, such as TNF-α and IL-1β^{36, 37}. C) Activation of the hypothalamic-pituitary-adrenocortical (HPA) axis leads to glucocorticoid (GC) release from the adrenal glands that exerts anti-inflammatory effects through binding of GC to cytosolic glucocorticoid receptor (GR) and inhibition of IL-6 release by monocytes.