Actualidades en la inmunopatología de la esclerosis múltiple

Abstract

La esclerosis múltiple es una enfermedad inflamatoria desmielinizante que afecta el sistema nervioso central. Su etiología es el resultado de una compleja interacción entre factores genéticos y ambientales que desencadenan una respuesta inmune desregulada, con la consiguiente inflamación y degeneración neuronal/axonal. La neuroinflamación se desencadena cuando los leucocitos periféricos migran al sistema nervioso central y liberan citocinas como interleucinas 1 y 6 (IL-1, IL-6) y factor de necrosis tumoral (TNF), que actúan sobre células residentes del mismo. El sistema inmune innato desempeña un papel importante en el inicio y progresión de la enfermedad, mediante la identificación de patrones moleculares asociados con patógenos y daño, que modulan las funciones efectoras y reguladoras de las células donde se expresan, para dirigir la respuesta inmune específica. Las células Th17 favorecen la disrupción de la barrera hematoencefálica, que permite la migración de leucocitos al sistema nervioso central y desencadena la cascada de la inflamación; el perfil Th1 (IL-1, IL-6) colabora para perpetuarla. La función de las células B es la producción de anticuerpos y citocinas (IL-6, IL-12 y TFN). Conocer la fisiopatología de la esclerosis múltiple permitirá desarrollar nuevas opciones terapéuticas que impacten en la historia natural de la enfermedad y su pronóstico.

A deep transcriptome meta-analysis reveals sex differences in multiple sclerosis

“…These alterations are closely related to innate immune responses and have been previously linked to MS and autoimmune diseases [85][86][87][88][89]. In contrast, males with MS exhibited transcriptome alterations related to immunomodulation of the lymphoid lineage (e.g., T cell subsets, natural killer cells, dendritic cells), affecting different features of these cells such activation, proliferation, or differentiation, which have a closer relation to adaptive immune responses [90][91][92]. Identifying T cell clones associated with human autoimmunity remains challenging and could have critical connotations for MS risk and outcomes.…”

A High MCT‐Based Ketogenic Diet Suppresses Th1 and Th17 Responses to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice by Inhibiting GSDMD and JAK2‐STAT3/4 Pathways

“…[61] The adoptive transfer of TH1 cells into naïve animals was shown to drive neuroinflammation, further supporting this notion. [62] Th2 and Treg cells have been shown to drive a decrease in inflammatory functions in microglial cells, promoting a neuroprotective microenvironment in MS. [63,64] In addition, Th17 cells favor the disruption of the blood-brain barrier, which enables leukocytes migration into the CNS and the triggering of the inflammatory cascade. [62,65] During T-cell signaling, Th1 cytokine IFN𝛾 influences differentiation to Th1 cells whereas Th2 cytokines, such as IL-4 foster Th2 cell differentiation.…”

“…[62] Th2 and Treg cells have been shown to drive a decrease in inflammatory functions in microglial cells, promoting a neuroprotective microenvironment in MS. [63,64] In addition, Th17 cells favor the disruption of the blood-brain barrier, which enables leukocytes migration into the CNS and the triggering of the inflammatory cascade. [62,65] During T-cell signaling, Th1 cytokine IFN𝛾 influences differentiation to Th1 cells whereas Th2 cytokines, such as IL-4 foster Th2 cell differentiation. [66] T-bet generally drives the differentiation of Th0 cells into Th1 cells, and GATA-3 promotes Th2 response.…”

A Deep Transcriptome Meta-Analysis Reveals Sex-based Molecular Differences in Multiple Sclerosis

“…These alterations are closely related to innate immune responses and have been previously linked to MS and autoimmune diseases [85–89]. In contrast, MS males presented immune alterations related to immunomodulation of lymphoid linage (e.g., T cell subsets, natural killer cells, dendritic cells), affecting activation, proliferation, or differentiation, which have a closer relation to adaptative immune responses [90–92]. Identifying T cell clones associated with human autoimmunity remains challenging and could have critical connotations in MS risk and outcomes.…”