Blockade of the T cell immunoglobulin and mucin domain protein 3 pathway exacerbates sepsis‐induced immune deviation and immunosuppression

Summary Sepsis is a life‐threatening condition, but the pathophysiological basis and biomarkers for the monitoring of sepsis and as targets for therapy remain to be determined. We have shown previously that T cell immunoglobulin and mucin domain protein 3 ( T im‐3), a negative immune regulator, is involved in the physiopathology of sepsis, but the underlying mechanisms remain unclear. In the present study, we showed that T im‐3 signalling modulated the response patterns of both macrophages and T helper cells in sepsis. Blockade of the T im‐3 pathway exacerbated sepsis‐induced proinflammatory macrophage responses and lymphocyte apoptosis during the early phase of sepsis, and enhanced the shift to anti‐inflammatory responses for both macrophages and T helper cells during the late phase of sepsis. T im‐3 signalling was found to regulate CD 80 and CD 86 expression on macrophages both in vivo and in vitro . Co‐culture of T cells with T im‐3 knock‐down macrophages led to a biased T helper type 2 ( T h2) response, partially explaining how T im‐3 signalling shapes inflammation patterns in vivo . Further studies on this pathway might shed new light on the pathogenesis of sepsis and suggest new approaches for intervention.