Publication: Mecanismos moleculares de la respuesta antiinflamatoria de macrófagos humanos
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2022-06-28
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Universidad Complutense de Madrid
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Abstract
Los macrófagos son las células responsables de orquestar la respuesta inmunológica, siendo efectores fundamentales del sistema inmunológico innato y actuando como puente entre este y las células del sistema inmunológico adquirido. Los macrófagos intervienen en un amplio abanico de procesos, que van desde la estimulación y la terminación de la respuesta inflamatoria del huésped a procesos de desarrollo y homeostasis tisular. Esta gran diversidad funcional solo puede desempeñarse gracias al extenso espectro de estados de polarización que los macrófagos pueden adquirir bajo la influencia de señales del microambiente tisular. De hecho, la desregulación de sus funciones efectoras puede dar lugar o favorecer patologías tan relevantes como los tumores, el COVID-19 o diversos trastornos autoinmunes e inflamatorios. Clásicamente, se ha considerado que los macrófagos pueden presentar dos estados de polarización opuestos, si bien esta división es una sobresimplificación. La presencia de factores como TNF-α, IFNγ o GM-CSF dota a los macrófagos de un perfil proinflamatorio, el cual se caracteriza por la expresión de moléculas coestimuladoras y la producción de citoquinas proinflamatorias, como IL-6, IL-12 o TNF-α. Por otra parte, citoquinas como IL-4, IL-13 o M-CSF hacen que los macrófagos adquieran un perfil antiinflamatorio y/o reparador, caracterizado por la producción de citoquinas antiinflamatorias como IL-10 o TGFβ. El estudio de las características transcripcionales de macrófagos antiinflamatorios, y de su respuesta a estímulos patogénicos, constituye el eje central de este trabajo...
Macrophages are responsible for orchestrating the immune response. They are fundamental effectors of the innate immune system and connect it to the acquired immune system. Macrophages are involved in a wide range of processes. They can stimulate and resolve inflammatory responses but are also involved in tissue development and homeostasis. Their functional diversity is reflected by the huge spectrum of polarization states acquired by macrophages in response to cues from the tissue environment. Of note, macrophage malfunction can give rise to clinically relevant pathologies such as tumors, COVID-19, and autoimmune and inflammatory disorders.Macrophages can acquire a wide spectrum of activation (polarization) states, although two opposite extremes of the spectrum (M1, pro-Th1/pro-inflammatory; M2, pro-Th2/reparative/anti-inflammatory) have been defined for simplicity. Pro-inflammatory macrophages appear in the presence of TNF-α, IFNγ or GM-CSF, they express high levels of co-stimulatory molecules, and produce pro-inflammatory cytokines, such as IL-6, IL-12 or TNF-α. On the other hand, IL-4, IL-13, or M-CSF prompt the acquisition of an anti-inflammatory functional profile in macrophages, in which they secrete anti-inflammatory cytokines, such as IL-10 or TGFβ. The study of the transcriptional signature of anti-inflammatory macrophages, and their responses towards pathogenic stimuli constitutes the central axis of this work...
Macrophages are responsible for orchestrating the immune response. They are fundamental effectors of the innate immune system and connect it to the acquired immune system. Macrophages are involved in a wide range of processes. They can stimulate and resolve inflammatory responses but are also involved in tissue development and homeostasis. Their functional diversity is reflected by the huge spectrum of polarization states acquired by macrophages in response to cues from the tissue environment. Of note, macrophage malfunction can give rise to clinically relevant pathologies such as tumors, COVID-19, and autoimmune and inflammatory disorders.Macrophages can acquire a wide spectrum of activation (polarization) states, although two opposite extremes of the spectrum (M1, pro-Th1/pro-inflammatory; M2, pro-Th2/reparative/anti-inflammatory) have been defined for simplicity. Pro-inflammatory macrophages appear in the presence of TNF-α, IFNγ or GM-CSF, they express high levels of co-stimulatory molecules, and produce pro-inflammatory cytokines, such as IL-6, IL-12 or TNF-α. On the other hand, IL-4, IL-13, or M-CSF prompt the acquisition of an anti-inflammatory functional profile in macrophages, in which they secrete anti-inflammatory cytokines, such as IL-10 or TGFβ. The study of the transcriptional signature of anti-inflammatory macrophages, and their responses towards pathogenic stimuli constitutes the central axis of this work...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, leída el 10-05-2022