Interleukin-6 signalling mediates Galectin-8 co-stimulatory activity of antigen-specific CD4 T-cell response.
Carabelli, J., Prato, C. A., Sanmarco, L. M., Aoki, M. P., Campetella, O. and Tribulatti, M. V.
Laboratorio de Inmunologia Molecular, Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin (UNSAM), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), San Martin, Buenos Aires, Argentina.
Universidad Nacional de Cordoba, Facultad de Ciencias Quimicas, Departamento de Bioquimica Clinica, Cordoba, Argentina.
Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI), Cordoba, Argentina.
Galectin-8 (Gal-8) is a mammalian lectin endowed with the ability to costimulate antigen-specific immune responses. We have previously demonstrated that bone marrow-derived dendritic cells produce high levels of IL-6 in response to Gal-8 stimulation. Since IL-6 is a pleiotropic cytokine that has a broad effect on cells of the immune system, in the present study we aimed to elucidate whether IL-6 was involved in Gal-8-dependent costimulatory signals during antigen recognition by specific CD4 T cells. To this aim, splenocytes from DO11.10 mice were incubated with a low dose of the cognate ovoalbumin peptide in combination with Gal-8. IL-6 was found significantly increased in cultures stimulated with Gal-8 alone or Gal-8 plus cognate peptide. Moreover, IL-6 signaling was triggered during Gal-8-induced costimulation as determined by phosphorylation of STAT3. IL-6 blockade by neutralizing monoclonal antibody precluded Gal-8 costimulatory activity but did not affect the antigen-specific TCR activation. Different subsets of dendritic cells, as well as macrophages and B cells, were identified as the cellular source of IL-6 during Gal-8-induced costimulation. To confirm that IL-6 mediated the Gal-8 costimulatory effect, antigen-presenting cells from IL-6-deficient or wild-type mice were co-cultured with purified CD4 T cells from OTII mice in the presence of cognate peptide and Gal-8. Notably, Gal-8-induced costimulation but not the antigen-specific response, was significantly impaired in the presence of IL-6-deficient antigen-presenting cells. Even more, exogenous IL-6 fully restored Gal-8-induced costimulation. Taken together, our results demonstrate that IL-6 signaling mediates the Gal-8 immune-stimulatory effect. This article is protected by copyright. All rights reserved.
Immunology : en prensa (2018)