Fernández, Miriam;
Monsalve, Eva M.;
López‐López, Susana;
Ruiz‐García, Almudena;
Mellado, Susana;
Caminos, Elena;
García‐Ramírez, José Javier;
Laborda, Jorge;
Tranque, Pedro;
Díaz‐Guerra, María José M.
Absence of Notch1 in murine myeloid cells attenuates the development of experimental autoimmune encephalomyelitis by affecting Th1 and Th17 priming
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Media type:
E-Article
Title:
Absence of Notch1 in murine myeloid cells attenuates the development of experimental autoimmune encephalomyelitis by affecting Th1 and Th17 priming
Contributor:
Fernández, Miriam;
Monsalve, Eva M.;
López‐López, Susana;
Ruiz‐García, Almudena;
Mellado, Susana;
Caminos, Elena;
García‐Ramírez, José Javier;
Laborda, Jorge;
Tranque, Pedro;
Díaz‐Guerra, María José M.
Description:
<jats:title>Abstract</jats:title><jats:p>Inhibition of Notch signalling in T cells attenuates the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Growing evidence indicates that myeloid cells are also key players in autoimmune processes. Thus, the present study evaluates the role of the Notch1 receptor in myeloid cells on the progression of myelin oligodendrocyte glycoprotein (MOG)<jats:sub>35‐55</jats:sub>‐induced EAE, using mice with a myeloid‐specific deletion of the <jats:italic>Notch1</jats:italic> gene (MyeNotch1KO). We found that EAE progression was less severe in the absence of <jats:italic>Notch1</jats:italic> in myeloid cells. Thus, histopathological analysis revealed reduced pathology in the spinal cord of MyeNotch1KO mice, with decreased microglia/astrocyte activation, demyelination and infiltration of CD4<jats:sup>+</jats:sup> T cells. Moreover, these mice showed lower Th1 and Th17 cell infiltration and expression of IFN‐γ and IL‐17 mRNA in the spinal cord. Accordingly, splenocytes from MyeNotch1KO mice reactivated in vitro presented reduced Th1 and Th17 activation, and lower expression of IL‐12, IL‐23, TNF‐α, IL‐6, and CD86. Moreover, reactivated wild‐type splenocytes showed increased <jats:italic>Notch1</jats:italic> expression, arguing for a specific involvement of this receptor in autoimmune T cell activation in secondary lymphoid tissues. In summary, our results reveal a key role of the Notch1 receptor in myeloid cells for the initiation and progression of EAE.</jats:p>