Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT2B –Dependent Activation of the Aryl Hydrocarbon Receptor

Autor: Catherine Béchade, Concha Nieto, Angel L. Corbí, Bárbara Alonso, Miguel A. Vega, Mateo de las Casas-Engel, Ignacio Rayo, Luc Maroteaux, Elena Izquierdo
Přispěvatelé: Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Fundació La Marató de TV3, Red de Investigación en Inflamación y Enfermedades Reumáticas (España), European Commission, Nieto, Concha [0000-0003-0790-3440], Izquierdo, Elena [0000-0002-3355-2798], Alonso, Bárbara [0000-0001-9973-4431], Béchade, Catherine [0000-0003-2070-2993], Maroteaux, Luc [0000-0002-9499-8603], Vega, Miguel A. [0000-0001-6151-4193], Corbí, Angel L. [0000-0003-1980-5733], Nieto, Concha, Izquierdo, Elena, Alonso, Bárbara, Béchade, Catherine, Maroteaux, Luc, Vega, Miguel A., Corbí, Angel L.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Cellular differentiation
medicine.medical_treatment
Immunology
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
03 medical and health sciences
0302 clinical medicine
medicine
Immunology and Allergy
Receptor
[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity
Transcription factor
5-HT receptor
030304 developmental biology
0303 health sciences
biology
Chemistry
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Aryl hydrocarbon receptor
Cell biology
Cytokine
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
biology.protein
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Serotonin
Signal transduction
030217 neurology & neurosurgery
Zdroj: Journal of Immunology
Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2020, pp.ji1901531. ⟨10.4049/jimmunol.1901531⟩
Digital.CSIC. Repositorio Institucional del CSIC
instname
Journal of Immunology, 2020, pp.ji1901531. ⟨10.4049/jimmunol.1901531⟩
ISSN: 0022-1767
1550-6606
Popis: 13 p.-7 fig.-2 fig. sup.-1 tab. supl.
Macrophages can either promote or resolve inflammatory responses, and their polarization state is modulated by peripheral serotonin (5-hydroxytryptamine [5-HT]). In fact, pro- and anti-inflammatory macrophages differ in the expression of serotonin receptors, with 5-HT2B and 5-HT7 expression restricted to M-CSF-primed monocyte-derived macrophages (M-MØ). 5-HT7 drives the acquisition of profibrotic and anti-inflammatory functions in M-MØ, whereas 5-HT2B prevents the degeneration of spinal cord mononuclear phagocytes and modulates motility of murine microglial processes. Because 5-HT2B mediates clinically relevant 5-HT-related pathologies (valvular heart disease, pulmonary arterial hypertension) and is an off target of anesthetics, antiparkinsonian drugs, and selective serotonin reuptake inhibitors, we sought to determine the transcriptional consequences of 5-HT2B engagement in human macrophages, for which 5-HT2B signaling remains unknown. Assessment of the effects of specific agonists and antagonist revealed that 5-HT2B engagement modifies the cytokine and gene signature of anti-inflammatory M-MØ, upregulates the expression of aryl hydrocarbon receptor (AhR) target genes, and stimulates the transcriptional activation of AhR. Moreover, we found that 5-HT dose dependently upregulates the expression of AhR target genes in M-MØ and that the 5-HT-mediated activation of AhR is 5-HT2B dependent because it is abrogated by the 5-HT2B-specific antagonist SB204741. Altogether, our results demonstrate the existence of a functional 5-HT/5-HT2B/AhR axis in human macrophages and indicate that 5-HT potentiates the activity of a transcription factor (AhR) that regulates immune responses and the biological responses to xenobiotics.
This work was supported by grants from Ministerio de Ciencia e Innovación (SAF2014-52423-R and SAF2017-83785-R) (to M.A.V. and Á.L.C.), 201619.31 from Fundació La Marató/TV3 (to Á.L.C.), and Red de Investigación en Enfermedades Reumáticas (RD16/0012/0007), and cofinanced by the European Regional Development Fund “A way to achieve Europe.” M.d.l.C.-E. and I.R. were funded by a Formación de Personal Investigador predoctoral fellowship (BES-2009-021465 and BES-2015-071337, respectively) from Ministerio de Ciencia e Innovación.
Databáze: OpenAIRE
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