Baricitinib Ameliorates Experimental Autoimmune Encephalomyelitis by Modulating the Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway
Open Access
- 13 April 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and a CD4+ T cell-mediated autoimmune disease. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is recognized as the major mechanism that regulates the differentiation and function of T helper (Th) 1 and Th17 cells, which are recognized as pivotal effector cells responsible for the development of EAE. We used baricitinib, a JAK 1/2 inhibitor, to investigate the therapeutic efficacy of inhibiting the JAK/STAT pathway in EAE mice. Our results showed that baricitinib significantly delayed the onset time, decreased the severity of clinical symptoms, shortened the duration of EAE, and alleviated demyelination and immune cell infiltration in the spinal cord. In addition, baricitinib treatment downregulated the proportion of interferon-γ+CD4+ Th1 and interleukin-17+CD4+ Th17 cells, decreased the levels of retinoic acid-related orphan receptor γ t and T-bet mRNA, inhibited lymphocyte proliferation, and decreased the expression of proinflammatory cytokines and chemokines in the spleen of mice with EAE. Furthermore, our results showed the role of baricitinib in suppressing the phosphorylation of STATs 1, 3, and 4 in the spleen of EAE mice. Therefore, our study demonstrates that baricitinib could potentially alleviate inflammation in mice with EAE and may be a promising candidate for treating MS.This publication has 64 references indexed in Scilit:
- JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated DiseaseImmunity, 2012
- Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)British Journal of Pharmacology, 2011
- Th1 versus Th17: Are T cell cytokines relevant in multiple sclerosis?Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2011
- Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal ResearchPLoS Biology, 2010
- Differentiation of Effector CD4 T Cell PopulationsAnnual Review of Immunology, 2010
- IL-17 and Th17 CellsAnnual Review of Immunology, 2009
- Janus kinases in immune cell signalingImmunological Reviews, 2009
- Late Developmental Plasticity in the T Helper 17 LineageImmunity, 2009
- T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosisImmunology, 2008
- Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector categoryThe Journal of Experimental Medicine, 2008