IL-6 Inhibition as a Therapeutic Target in Aged Experimental Autoimmune Encephalomyelitis
Dema, María (Vall d'Hebron Institut de Recerca (VHIR))
Eixarch, Herena (Vall d'Hebron Institut de Recerca (VHIR))
Castillo Juárez, Mireia (Vall d'Hebron Institut de Recerca (VHIR))
Montalban, Xavier (Vall d'Hebron Institut de Recerca (VHIR))
Espejo, Carmen (Vall d'Hebron Institut de Recerca (VHIR))
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Multiple sclerosis (MS) onset at an advanced age is associated with a higher risk of developing progressive forms and a greater accumulation of disability for which there are currently no effective disease-modifying treatments. Immunosenescence is associated with the production of the senescence-associated secretory phenotype (SASP), with IL-6 being one of the most prominent cytokines. IL-6 is a determinant for the development of autoimmunity and neuroinflammation and is involved in the pathogenesis of MS. Herein, we aimed to preclinically test the therapeutic inhibition of IL-6 signaling in experimental autoimmune encephalomyelitis (EAE) as a potential age-specific treatment for elderly MS patients. Young and aged mice were immunized with myelin oligodendrocyte protein (MOG) and examined daily for neurological signs. Mice were randomized and treated with anti-IL-6 antibody. Inflammatory infiltration was evaluated in the spinal cord and the peripheral immune response was studied. The blockade of IL-6 signaling did not improve the clinical course of EAE in an aging context. However, IL-6 inhibition was associated with an increase in the peripheral immunosuppressive response as follows: a higher frequency of CD4 T cells producing IL-10, and increased frequency of inhibitory immune check points PD-1 and Tim-3 on CD4 + T cells and Lag-3 and Tim-3 on CD8 + T cells. Our results open the window to further studies aimed to adjust the anti-IL-6 treatment conditions to tailor an effective age-specific therapy for elderly MS patients.
Ajuts:	Instituto de Salud Carlos III PI18/01146
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Experimental autoimmune encephalomyelitis ; IL-6 ; Immunosenescence ; Ageing ; Innate immunity ; Multiple sclerosis
Publicat a:	International journal of molecular sciences, Vol. 25 (june 2024) , ISSN 1422-0067

DOI: 10.3390/ijms25126732
PMID: 38928437

13 p, 1.6 MB

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