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Tag: MKK3 (Page 1 of 2)

Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis

Ivana Nikolić, Irene Ruiz-Garrido, María Crespo, Rafael Romero-Becerra, Luis Leiva-Vega, Alfonso Mora, Marta León, Elena Rodríguez, Magdalena Leiva, Ana Belén Plata-Gómez, Maria Beatriz Alvarez Flores, Jorge L Torres, Lourdes Hernández-Cosido, Juan Antonio López, Jesús Vázquez, Alejo Efeyan, Pilar Martin, Miguel Marcos & Guadalupe Sabio.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established.

Reduction of fat mass of mice lacking MKK3/6 as seen by MRI (Image: Ivana Nikolić).

Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients.

Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

CICERONE program 2019 for Masters and advanced undergraduate students

As in previous years, our group is open to master and advanced undergraduate students for extending their scientific training through hands-on experience in our laboratory during the summer recess (1 July – 30 September). In addition to carrying out a supervised research project, the students will also attend CNIC seminars.

The aim of the CICERONE program is to give university students first-hand knowledge of biomedical research so that they can make more informed choices about the possibility of pursuing a scientific career.

To apply, you must register at CNIC website before 15 April 2019.

Link Size
2019 Guidelines 348 KB
Document of acceptance 1.53 MB
Call extract from BOE 171 KB

For the 2019 call, we are offering the following research projects:

  • Role of p38MAPK in metabolic diseases: Metabolic syndrome is a medical disorder defined by the co‐occurrence of obesity, impaired glucose tolerance, dyslipidemia and hypertension. Stress activated protein kinases have been shown to control both obesity by itself and diabetes associated to obesity. These stress kinases are activated by several MAPK activated kinases (MKK). We want to investigate the role of MKK3 in this process and the molecular mechanism by which this kinase could affect diabetes.
  • p38MAPK in heart physiology: The p38MAPK pathway transduces a variety of extracellular signals regulating cellular responses to stress, being implicated in cell proliferation, differentiation and apoptosis. Its implication in the development of human diseases it is being deeply studied. Four p38MAPK family members have been identified: p38α, β, γ and δ. Preliminary data from our laboratory show that these kinases may control cytokine production during acute and chronic inflammatory processes. Moreover, studies with genetically modified mice made in our laboratory confirm that p38MAPKs have a role in the development of the heart. Our main objective is to determine if the regulation of the p38MAPK signalling pathway could have beneficial effects in the cardiac response to exercise.

II reunión científica Immunothercan-CM (13 December 2018)

El próximo jueves 13 de diciembre de 2018 tendrá lugar la segunda reunión científica del consorcio Immunothercan-CM, en el Centro Nacional de Biotecnología (Campus Universidad Autónoma).

En esta reunión, los investigadores pre y postdoctorales de los distintos grupos presentarán los últimos avances en los proyectos que se desarrollan en el marco del consorcio. Además, se discutirán aspectos que fomenten la colaboración entre los grupos.

Immunothercan

Programa de la II reunión científica Immunothercan-CM

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