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Review
. 2018 Jun 25;9:1440.
doi: 10.3389/fimmu.2018.01440. eCollection 2018.

Neuroendocrine Control of Macrophage Development and Function

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Free PMC article
Review

Neuroendocrine Control of Macrophage Development and Function

Arnon Dias Jurberg et al. Front Immunol. .
Free PMC article

Abstract

Macrophages carry out numerous physiological activities that are essential for both systemic and local homeostasis, as well as innate and adaptive immune responses. Their biology is intricately regulated by hormones, neuropeptides, and neurotransmitters, establishing distinct neuroendocrine axes. The control is pleiotropic, including maturation of bone marrow-derived myeloid precursors, cell differentiation into functional subpopulations, cytotoxic activity, phagocytosis, production of inflammatory mediators, antigen presentation, and activation of effector lymphocytes. Additionally, neuroendocrine components modulate macrophage ability to influence tumor growth and to prevent the spreading of infective agents. Interestingly, macrophage-derived factors enhance glucocorticoid production through the stimulation of the hypothalamic-pituitary-adrenal axis. These bidirectional effects highlight a tightly controlled balance between neuroendocrine stimuli and macrophage function in the development of innate and adaptive immune responses. Herein, we discuss how components of neuroendocrine axes impact on macrophage development and function and may ultimately influence inflammation, tissue repair, infection, or cancer progression. The knowledge of the crosstalk between macrophages and endocrine or brain-derived components may contribute to improve and create new approaches with clinical relevance in homeostatic or pathological conditions.

Keywords: glucocorticoids; hormones; macrophages; monocytes; neuroendocrine system; neurotransmitters; stress.

Figures

Figure 1
Figure 1
Neuroendocrine communication on macrophages. Schematic representation listing selected receptors (and their ligands) found in macrophages. Receptors were grouped into classes, as indicated. Abbreviations: (P)RR, (pro)renin receptor; 5-HTR, serotonin receptor; ACTH, adrenocorticotropic hormone; AdipoRs, adiponectin receptors; AR, androgen receptor; AT1, angiotensin II receptor type 1; AVP, arginine vasopressin or antidiuretic hormone; AVPR2, arginine vasopressin receptor 2; BB2, bombesin receptor; CCK, cholecystokinin; CCK1/2R, cholecystokinin receptor 1/2, respectively; c-mpl, myeloproliferative leukemia protein; CO, carbon monoxide; CTR, calcitonin receptor; cysLT1-R, cysteinyl leukotriene receptor 1; DHT, dihydrotestosterone; DR, dopamine receptor; EP2, prostaglandin E2 receptor 2; EP4, prostaglandin E2 receptor 4; Epi, epinephrine; EpoR, erythropoietin receptor; ER, estrogen receptor; FSH, follicle-stimulating hormone; FSHR, follicle-stimulating hormone receptor; GABA, gamma-aminobutyric acid; GABAA/B, GABAA-receptor and GABAB-receptor, respectively; GC, glucocorticoids; GH, growth hormone; GHR, growth hormone receptor; GHSR, growth hormone secretagogue receptor (also known as ghrelin receptor); GLP-1, glucagon-like peptide-1; GLP-1R, Glucagon-like peptide-1 receptor; GR, glucocorticoid receptor; GRP, gastrin-releasing peptide; hCG, human chorionic gonadotropin; hPL, human placental lactogen; IGF, insulin-like growth factor; IR, insulin receptor; LepR, leptin receptor; LH, luteinizing hormone; LTD4, leukotriene D4; mAChR, muscarinic acetylcholine receptor; MC1/3, melanocortin 1/3 receptor, respectively; MR, mineralocorticoid receptor; nAChR, nicotinic acetylcholine receptor; NE, norepinephrine; NGF, nerve growth factor; NK-1R, neurokinin 1 receptor; NPRs, natriuretic peptide receptors; NPY, neuropeptide Y; NR3C3, nuclear receptor subfamily 3, group C, member 3; OTXR, oxytocin receptor; p75NTR, neurotrophin receptor p75; PAC1, pituitary adenylate cyclase-activating polypeptide type I receptor; PACAP, pituitary adenylate cyclase-activating peptide; PGE2, prostaglandin 2; PR, progesterone receptor; PRLR, prolactin receptor; PYY, Peptide YY; RAR, retinoic acid receptor; sGC, soluble guanylyl cyclase; Soluble guanylyl cyclase (GC-1); SST2, somatostatin receptor type 2; TR, thyroid hormone receptor; TrkA, transmembrane tyrosine kinase; VDR, vitamin D receptor; VIP, vasoactive intestinal peptide; VPAC1/2, vasoactive intestinal peptide receptor 1/2, respectively; Y1/2/5, neuropeptide Y receptor type 1/2/5, respectively; α/β-ARs, α/β-adrenergic receptors; α-MSH, melanocyte-stimulating hormone.
Figure 2
Figure 2
Neuroendocrine-associated genes are differentially expressed during macrophage differentiation. Heatmap of RNA-Seq profile filtered by keywords from Mass et al. (9) depicting hierarchically clustered relative gene expression (log2) in erythro-myeloid progenitors, pre-macrophages (preMacs), and macrophages. Levels of expression are represented by colors in which red, white, and blue indicate high, intermediate, and low intensities, respectively.
Figure 3
Figure 3
The influence of glucocorticoids on monocytes and macrophages. Glucocorticoids may play opposing effects on monocytes and macrophages depending on theirs levels and time of exposure (top). A graphical representation depicts these effects on monocyte trafficking into tissues, macrophage polarization, and phagocytosis (bottom). A short and low increase in glucocorticoid levels (left) stimulates monocyte extravasation into the injured tissue, while high and long-lasting levels of glucocorticoids (right) inhibit monocyte proliferation and extravasation, as well as drive macrophage polarization into anti-inflammatory phenotypes that may produce extracellular matrix or stimulate the engulfment of apoptotic cells. All these phenomena are also influenced by cytokines present in the milieu.

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