Role of Cytokines, Chemokines and IFN-γ+ IL-17+ Double-Positive CD4+ T Cells in Patients with Multiple Sclerosis

Marlos Aureliano Dias de Sousa; Chamberttan Souza Desidério; Jonatas da Silva Catarino; Rafael Obata Trevisan; Djalma Alexandre Alves da Silva; Vinicius Ferreira Resende Rocha; Weslley Guimarães Bovi; Rodolfo Pessato Timoteo; Renata Cristina Franzon Bonatti; Alex Eduardo da Silva; Alfredo Leboreiro Fernandez; Helioswilton Sales-Campos; Virmondes Rodrigues Junior; Marcos Vinicius da Silva; Carlo José Freire de Oliveira

doi:10.3390/biomedicines10092062

Role of Cytokines, Chemokines and IFN-γ⁺ IL-17⁺ Double-Positive CD4⁺ T Cells in Patients with Multiple Sclerosis

Biomedicines. 2022 Aug 24;10(9):2062. doi: 10.3390/biomedicines10092062.

Authors

Marlos Aureliano Dias de Sousa^{1

2}, Chamberttan Souza Desidério¹, Jonatas da Silva Catarino³, Rafael Obata Trevisan¹, Djalma Alexandre Alves da Silva¹, Vinicius Ferreira Resende Rocha¹, Weslley Guimarães Bovi¹, Rodolfo Pessato Timoteo¹, Renata Cristina Franzon Bonatti², Alex Eduardo da Silva², Alfredo Leboreiro Fernandez², Helioswilton Sales-Campos⁴, Virmondes Rodrigues Junior¹, Marcos Vinicius da Silva¹, Carlo José Freire de Oliveira^{1

5}

Affiliations

¹ Department of Immunology, Microbiology and Parasitology, Federal University of Triângulo Mineiro, Uberaba 38025-180, MG, Brazil.
² Department of Neurology, Federal University of Triângulo Mineiro, Uberaba 38025-180, MG, Brazil.
³ Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
⁴ Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiania 74605-050, GO, Brazil.
⁵ Laboratory of Immunology and Bioinformatics, Universidade Federal do Triângulo Mineiro, Rua Vigário Carlos, 100, 8th Floor, Uberaba 38025-350, MG, Brazil.

Abstract

Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4⁺ T cells that produce cytokines and chemokines. This participation is important to find markers for the diagnosis and progression of the disease. In our work, we evaluated the profile of cytokines and chemokines, as well as the production of double positive CD4⁺ T cells for the production of IFNγ IL-17 in patients with multiple sclerosis, at different stages of the disease and undergoing different treatments. We found that relapsing-remitting patients had a significant increase in IL-12 production. About IL-5, its production showed significantly higher levels in secondarily progressive patients when compared to relapsing-remitting patients. IFN-γ production by PBMCs from secondarily progressive patients showed significantly higher levels. This group also had a higher percentage of CD4⁺ IFNγ⁺ IL-17⁺ T cells. The combination of changes in certain cytokines and chemokines together with the presence of IFNγ⁺ IL-17⁺ double positive lymphocytes can be used to better understand the clinical forms of the disease and its progression.

Keywords: Multiple sclerosis; chemokine; cytokine; double-positive CD4+ T cells.

Grants and funding

This study was supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico. The funding sources were not involved in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.