In the present study we report for the first time that ICOS-ICOSL axis may play a role in regulation of uncontrolled inflammation and organ injury induced by sepsis and that treatment of septic mice with ICOS-Fc may represent a novel immunomodulatory pharmacological approach that can simultaneously counteract both sepsis-induced hyperinflammation and immunosuppression. This evidence concerns the gene ICOSLG and Sepsis.