Publication: Perfil transcripcional de macrófagos antiinflamatorios humanos en condiciones de homeostasis, activación y patológicas
Loading...
Official URL
Full text at PDC
Publication Date
2017-11-27
Authors
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad Complutense de Madrid
Citations
Exportar
Abstract
Los macrófagos son células del sistema inmune innato que exhiben una gran heterogeneidad fenotípica y funcional, lo que les confiere la capacidad de detectar y responder con precisión a las necesidades de su microambiente. La diferenciación y funciones de los macrófagos dependen de la integración de las señales proporcionadas por su ontogenia, el tejido donde se encuentren, la microbiota, el metabolismo y la potencial presencia de estímulos patógenicos. Los macrófagos juegan un papel esencial en desarrollo, homeostasis e inflamación y, por ello, la desregulación de funciones de los macrófagos lleva a la aparición y mantenimiento de numerosas patologías de base inflamatoria. En consecuencia, la determinación de la base molecular de la heterogeneidad funcional de macrófagos debería allanar el camino para el desarrollo de terapias anti-inflamatorias específicas de tejido. Los macrófagos son capaces de iniciar y resolver la inflamación. La activación de macrófagos se basa en el reconocimiento de patrones moleculares asociados a patógenos (PAMP) y de peligro (DAMP) que llevan a cabo receptores como los miembros de la familia de TLR,. Dependiendo de la ontogenia, el entorno y naturaleza de las señales previas recibidas por los macrófagos, la respuesta a un estímulo puede ser pro- o anti-inflamatoria. La primera es característica de macrófagos expuestos a GM-CSF o IFNγ y resulta en la producción de TNF-α, IL-12, IL-6 e IL-23. La respuesta anti-inflamatoria, en cambio, es específica de macrófagos expuestos a M-CSF, IL-4 o glucocorticoides y conlleva la secreción de IL-10. La respuesta pro-inflamatoria de macrófagos ha sido ampliamente estudiada, en contraposición al escaso conocimiento disponible sobre la activación de macrófagos anti-inflamatorios, especialmente en humanos...
Macrophages are cells of the innate immune system that exhibit a huge phenotypic and functional heterogeneity, what gives macrophages the ability to sense and respond accurately to the needs of their microenvironment. Thus, macrophage differentiation and functions are dependent on the integration of cues provided by their ontogeny, surrounding tissue, microbiota, metabolism and pathogens. In line with their functional plasticity, macrophages are able to both initiate and resolve inflammation. Besides, macrophages have essential roles in development, homeostasis and inflammation and, consequently, deregulation of macrophage functions leads to the onset and maintenance of numerous chronic inflammatory pathologies. Therefore, determination of the molecular basis of the macrophage functional heterogeneity should pave the way for the development of tissue-specific anti-inflammatory therapies. Macrophage activation relies on the recognition of pathogen- and danger-associated molecular patterns from exogenous and endogenous factors by a variety of receptors, like TLRs. Depending on the nature of previous cues received by macrophages, the response to activating stimuli may be pro- or antiinflammatory. The former is characteristic of macrophages exposed to GM-CSF or IFNγ and results in the production of TNF-α, IL-12, IL-6 and IL-23. The latter is specific for macrophages exposed to M-CSF, IL-4 or glucocorticoids and leads to the secretion of IL-10. Unlike the macrophage pro-inflammatory response, which has been extensively studied, scarce knowledge is currently available on the activation of anti-inflammatory macrophages, especially in humans. To address this issue, we have thoroughly analyzed the transcriptome of TLR-activated, human M-CSF-polarized anti-inflammatory macrophages (M-MØ)...
Macrophages are cells of the innate immune system that exhibit a huge phenotypic and functional heterogeneity, what gives macrophages the ability to sense and respond accurately to the needs of their microenvironment. Thus, macrophage differentiation and functions are dependent on the integration of cues provided by their ontogeny, surrounding tissue, microbiota, metabolism and pathogens. In line with their functional plasticity, macrophages are able to both initiate and resolve inflammation. Besides, macrophages have essential roles in development, homeostasis and inflammation and, consequently, deregulation of macrophage functions leads to the onset and maintenance of numerous chronic inflammatory pathologies. Therefore, determination of the molecular basis of the macrophage functional heterogeneity should pave the way for the development of tissue-specific anti-inflammatory therapies. Macrophage activation relies on the recognition of pathogen- and danger-associated molecular patterns from exogenous and endogenous factors by a variety of receptors, like TLRs. Depending on the nature of previous cues received by macrophages, the response to activating stimuli may be pro- or antiinflammatory. The former is characteristic of macrophages exposed to GM-CSF or IFNγ and results in the production of TNF-α, IL-12, IL-6 and IL-23. The latter is specific for macrophages exposed to M-CSF, IL-4 or glucocorticoids and leads to the secretion of IL-10. Unlike the macrophage pro-inflammatory response, which has been extensively studied, scarce knowledge is currently available on the activation of anti-inflammatory macrophages, especially in humans. To address this issue, we have thoroughly analyzed the transcriptome of TLR-activated, human M-CSF-polarized anti-inflammatory macrophages (M-MØ)...
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular I, leída el 16-12-2016