Elevated proportion of TLR2- and TLR4-expressing Th17-like cells and activated memory B cells was associated with clinical activity of cerebral cavernous malformations

Journal of Neuroinflammation

Marcos Octávio S. D. Cafasso¹  Clarice Monteiro²  Priscila M. Sacramento²  Lana M. Lopes²  Camilla Castro²  Hugo A. A. Oyamada²  Cleonice A. M. Bento³  Joana Hygino⁴  Jorge Paes Barreto Marcondes de Souza⁵  Soniza Vieira Alves-Leon⁶  Gustavo da Fontoura Galvão⁷ 

[1] Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Frei Caneca 94, 20261-040, Rio de Janeiro, RJ, Brazil;Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Frei Caneca 94, 20261-040, Rio de Janeiro, RJ, Brazil;Post-Graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Frei Caneca 94, 20261-040, Rio de Janeiro, RJ, Brazil;Post-Graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;Post-Graduate Program in Neurology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Frei Caneca 94, 20261-040, Rio de Janeiro, RJ, Brazil;Post-Graduate Program in Neurology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;Post-Graduate Program in Neurology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;Service of Neurosurgery, University Hospital of the Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil;Post-Graduate Program of Surgical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Post-Graduate Program in Neurology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;Translational Neuroscience Laboratory (LabNet), University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;Service of Neurosurgery, University Hospital of the Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil;

关键词: Cerebral cavernous malformations;    T cells;    Th17 cells;    TLR;    Cytokines;    B cells;    LPS;   

DOI  :  10.1186/s12974-022-02385-2

来源: Springer

【 摘 要 】

BackgroundRecent evidences have suggested the involvement of toll-like receptor (TLR)-4 in the pathogenesis of cerebral cavernous malformations (CCM). Elevated frequency of TLR+T-cells has been associated with neurological inflammatory disorders. As T-cells and B-cells are found in CCM lesions, the objective of the present study was to evaluate the cytokine profile of T-cells expressing TLR2 and TLR4, as well as B-cell subsets, in asymptomatic (CCMAsympt) and symptomatic (CCMSympt) patients.MethodsFor our study, the cytokine profile from TLR2+ and TLR4+ T-cell and B-cell subsets in CCMAsympt and CCMSympt patients was investigated using flow cytometry and ELISA. T-cells were stimulated in vitro with anti-CD3/anti-CD28 beads or TLR2 (Pam3C) and TLR4 (LPS) ligands.ResultsCCMSymptc patients presented a higher frequency of TLR4+(CD4+ and CD8+) T-cells and greater density of TLR4 expression on these cells. With regard to the cytokine profile, the percentage of TLR2+ and TLR4+ Th17 cells was higher in CCMSympt patients. In addition, an elevated proportion of TLR4+ Tc-1 cells, as well as Tc-17 and Th17.1 cells expressing TLR2 and TLR4, was observed in the symptomatic patients. By contrast, the percentage of TLR4+ IL-10+CD4+ T cells was higher in the CCMAsympt group. Both Pam3C and LPS were more able to elevate the frequency of IL-6+CD4+T cells and Th17.1 cells in CCMSympt cell cultures. Furthermore, in comparison with asymptomatic patients, purified T-cells from the CCMSympt group released higher levels of Th17-related cytokines in response to Pam3C and, mainly, LPS, as well as after activation via TCR/CD28. Concerning the B-cell subsets, a higher frequency of memory and memory activated B-cells was observed in CCMSympt patients.ConclusionsOur findings reveal an increase in circulating Th17/Tc-17 cell subsets expressing functional TLR2 and, mainly, TLR4 molecules, associated with an increase in memory B-cell subsets in CCM patients with clinical activity of the disease.

【 授权许可】

CC BY