Group Leader/s

 

intro

During the last ten years, the research group led by Dr. Angel Luis Corbí and Dr. Miguel Vega Palacios (“Myeloid Cell Biology Laboratory”) has been actively involved in determining the molecular mechanisms underlying the acquisition of pro-inflammatory and anti-inflammatory effector functions by human macrophages. The most relevant achievements of the group in the last years include: 1) the identification of gene sets that specifically mark human macrophages in inflammatory disorders (rheumatoid arthritis, tumors); 2)  the identification of genes expressed by human anti-inflammatory macrophages under physiological and pathological settings (HMOX1, FOLR2, CD209, CCL2, HTR2B); 3) the demonstration of the macrophage re-programming ability of Activin A, CCL2, Serotonin and Intravenous Immunoglobulins; 4) the identification of the role of the transcription factors MAFB and MAF in macrophage re-programming and the control of cytokine and chemokine expression.

The group has led the Network “ARTRITIS REUMATOIDE: MECANISMOS FISIOPATOLÓGICOS E IDENTIFICACIÓN DE POSIBLES DIANAS TERRAPEÚTICAS“ (RAPHYME) since 2012, and belongs to ISCIII-funded RETICS “Red de Investigación en Enfermedades Reumáticas” (RIERI) since 2012. The group has been funded by consecutive projects from competitive calls from MCYT/MICIIN/MINECO since 1990, and has also led projects funded by FIS, Comunidad de Madrid, private foundations (Mutua Madrileña, FIPSE, Fundación TV3 La Marató, Fundación BBVA) and major projects from Genoma España (MEICA project). Reagents generated during the research activity of the group have been transferred to the productive sector (monoclonal antibodies against DC-SIGN and LSECtin licensed to Santa Cruz Biotechnology and Serotec).

 

Vega MA, Simón Fuentes M,Gonzalez de la Aleja A, Nieto C, Colmenares M, Herrero C, Domínguez-Soto A, Corbí AL.  [2020]. MAFB and MAF transcription factors as macrophage checkpoints for COVID-19 severity. Front Immunol, in press, 2020

Cuevas VD, Anta L, Samaniego R, Orta-Zavalza E, Vladimir de la Rosa J, Baujat G, Domínguez-Soto Á, Sánchez-Mateos P, Escribese MM, Castrillo A, Cormier-Daire V, Vega MA, Corbí ÁL.
 [2017]. 
MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis. J Immunol. 2017 Mar 1;198(5):2070-2081

Soler Palacios B, Nieto C, Fajardo P, González de la Aleja A, Andrés N, Dominguez-Soto A, Lucas P, Cuenda A, Rodríguez-Frade JM, Martínez-A C, Villares R, Corbí AL*, Mellado M*.  [2020]. Growth hormone reprograms macrophages towards an anti-inflammatory and reparative profile in a MAFB-dependent manner. J Immunol. 2020 Aug 1;205(3):776-788.

Nieto C, Rayo I, de Las Casas-Engel M, Izquierdo E, Alonso B, Béchade C, Maroteaux L, Vega MA, Corbí ÁL.  [2020]. Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT 2B-Dependent Activation of the Aryl Hydrocarbon Receptor. J Immunol. 2020 May 15;204(10):2808-2817

Domínguez-Soto Á, Usategui A, Casas-Engel ML, Simón-Fuentes M, Nieto C, Cuevas VD, Vega MA, Luis Pablos J, Corbí AL.  [2017]. Serotonin drives the acquisition of a profibrotic and anti-inflammatory gene profile through the 5-HT7R-PKA signaling axis. Sci Rep. 2017 Nov 7;7(1):14761.

Domínguez-Soto Á, Simón-Fuentes M, de Las Casas-Engel M, Cuevas VD, López-Bravo M, Domínguez-Andrés J, Saz-Leal P, Sancho D, Ardavín C, Ochoa-Grullón J, Sánchez-Ramón S, Vega MA, Corbí AL.  [2018]. IVIg Promote Cross-Tolerance against Inflammatory Stimuli In Vitro and In Vivo. J Immunol. 2018 Jul 1;201(1):41-52

Riera-Borrull M, Cuevas VD, Alonso B, Vega MA, Joven J, Izquierdo E, Corbí AL.  [2017]. Palmitate Conditions Macrophages for Enhanced Responses toward Inflammatory Stimuli via JNK Activation. J Immunol. 2017 Dec 1;199(11):3858-3869

Aguilera-Montilla N, Chamorro S, Nieto C, Sánchez-Cabo F, Dopazo A, Fernández-Salguero PM, Rodríguez-Fernández JL, Pello OM, Andrés V, Cuenda A, Alonso B, Domínguez-Soto A, Sánchez-Ramón S, Corbí AL  [2013]. Aryl hydrocarbon receptor contributes to the MEK/ERK-dependent maintenance of the immature state of human dendritic cells. BLOOD. 121: e108-e117

Elena Sierra-Filardi, Amaya Puig-Kröger, Francisco J. Blanco, Concha Nieto, Rafael Bragado, M. Isabel Palomero, Carmelo Bernabéu, Miguel A. Vega, and Angel L. Corbi  [2011]. Activin A skews macrophage polarization by promoting a pro-inflammatory phenotype and inhibiting the acquisition of anti-inflammatory macrophage markers. Blood

 

Funding

1.- Dendritic cell differentiation: Role of cell adhesion in dendritic cellspecific transcription and analysis of expression and functional activities of DC-SIGN (CICYT, SAF2002-04615-C02-01, 2003-2006).

2.- Structural and Functional variability of DC-SIGN: Correlation with susceptibility to HIV and M. tuberculosis infection (FIPSE 36422/03). (FIPSE, 2004-2007).

3.- Effects of probiotics and biogenic amines on the phenotypic and functional properties of human dendritic cells and macrophages (CICYT, AGL2004-02148, 2004-2007; BIAMFOOD UE project, 7th Framework prog. 2007-2010).

4.- Gene expression profiling during differentiation and maturation of human dendritic cells (CICYT, GEN2003-20649-CO6-01, 2004-2007).

5.- DC-SIGN: A pathogen receptor involved in immunesurveillance (CAM, GR/SAL/0638/2004, 2005).

6.- Diferenciación y maduración de células dendríticas: Implicación de los factores de transcripción RUNX3 y PU.1, y actividades funcionales de DC-SIGN que determinan la susceptibilidad a la infección por HIV y otros patógenos (SAF2005-00021)

7.- Base molecular de la actividad pro-oncogénica y supresora de tumores del regulador transcripcional RUNX3 (Mutua Madrileña Automovilista)

8.- Activación de macrófagos: Identificación de moléculas implicadas en la adquisición de funciones efectoras proinflamatorias y anti-inflamatorias (BFU2008-01493).

9.- Molecular and cellular mechanisms in chronic inflammatory and autoinmmune diseases (MEICA project, 2009-2011).

10.- Análisis de los factores del sistema inmunitario innato implicados en la respuesta a la infección por el virus Influenza A (N1H1) V2009 (FIS, GR09/0013).

11.- Expression and function of polysialic acid on dendritic cells (FIS, PI07/0887, 2008-2010)

12.- Characterization of neuropilin-2 and the polysialyltransferase ST8SiaIV as potential therapeutic targets for control if immunity and cancer (FIS, PI10/00304, 2011-2013)

13.- Mecanismos moleculares de la polarización pro- y anti-inflamatoria de macrófagos humanos (SAF2011-23801)

14.- Artritis reumatoide: mecanismos fisiopatológicos e identificación de posibles dianas terapéuticas (S2010/BMD-2350, RAPHYME)

15.- Modulatory actions of Activin A and Serotonin on macrophage activation and inflammatory pathologies (SAF2014-52423-R)

16.- Selective targeting of inflammatory functions of fat-activated macrophages for the treatment of obesity-associated type-2 diabetes (Fundación TV3/ La Marató 22/C/2016).

17.- Discovering molecular targets for inflammatory chronic diseases through dissection of the macrophage re-programming ability of MAFB, Serotonin, and Intravenous Immunoglobulins (SAF2017-83785-R).

18.- Human macrophage activation in COVID-19: involvement of MAF and MAFB in the cytokine storm triggered upon SARS-CoV-2 infection and identification of novel prognostic biomarkers (Fundación BBVA).

 

More info

Summary Macrophage re-programming

 

Graphical Abstracts of on-going projects

LXR role in macrophage re-programming

Macrophage re-programming by serotonin: mechanisms