IL-27-mediated hematopoietic dysregulation exacerbates disease severity in Severe Fever with Thrombocytopenia Syndrome Virus infection 3316

Description Severe Fever with Thrombocytopenia Syndrome (SFTS) is a life-threatening tick-borne viral infection characterized by high fever, thrombocytopenia, and severe inflammation, with no effective treatments currently available. Through comprehensive analysis of bone marrow and peripheral blood mononuclear cells from SFTS patients, and validation in a mouse model, we identified IL-27 as a key driver of disease progression. Elevated IL-27 levels promote emergency hematopoiesis and impair protective B cell development and antibody production, resulting in worsened inflammation and ineffective viral control. IL-27 induction in monocytes and B cells triggers a vicious inflammatory cycle, exacerbating the severity of SFTS. Neutralizing IL-27 in the mouse model significantly improved survival, reduced viral loads, and restored anti-viral immunity, highlighting IL-27 as a promising therapeutic target for SFTS.