Interleukin-6 signaling mediates Galectin-8 costimulatory activity of antigen-specific CD4 T cell response

CARABELLI, J; PRATO, CA; SANMARCO, LM; AOKI, MP; CAMPETELLA, O; TRIBULATTI, MV

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2018

0019-2805

Galectin-8 (Gal-8) is a mammalian lectin endowed withthe ability to costimulate antigen-specific immune responses. We havepreviously demonstrated that bone marrow-derived dendritic cells produce highlevels of IL-6 in response to Gal-8 stimulation. Since IL-6 is a pleiotropiccytokine that has a broad effect on cells of the immune system, in the presentstudy we aimed to elucidate whether IL-6 was involved in Gal-8-dependent costimulatorysignals during antigen recognition by specific CD4 T cells. To this aim, splenocytesfrom DO11.10 mice were incubated with a low dose of the cognate ovoalbuminpeptide in combination with Gal-8. IL-6 was found significantly increased in culturesstimulated with Gal-8 alone or Gal-8 plus cognate peptide. Moreover, IL-6signaling was triggered during Gal-8-induced costimulation as determined by phosphorylationof STAT3. IL-6 blockade by neutralizing monoclonal antibody precluded Gal-8costimulatory activity but did not affect the antigen-specific TCR activation. Differentsubsets of dendritic cells, as well as macrophages and B cells, were identifiedas the cellular source of IL-6 during Gal-8-induced costimulation. To confirmthat IL-6 mediated the Gal-8 costimulatory effect, antigen-presenting cellsfrom IL-6-deficient or wild-type mice were co-cultured with purified CD4 Tcells from OTII mice in the presence of cognate peptide and Gal-8. Notably, Gal-8-inducedcostimulation but not the antigen-specific response, was significantly impairedin the presence of IL-6-deficient antigen-presenting cells. Even more, exogenousIL-6 fully restored Gal-8-induced costimulation. Taken together, our results demonstratethat IL-6 signaling mediates the Gal-8 immune-stimulatory effect.