Blockade of the T cell immunoglobulin and mucin domain protein 3 pathway exacerbates sepsis-induced immune deviation and immunosuppression. (1st October 2014)

• Record Type: Journal Article
• Authors: Zhao, Z; Jiang, X; Kang, C; Xiao, Y; Hou, C; Yu, J; Wang, R; Xiao, H; Zhou, T; Wen, Z; Feng, J; Chen, G; Ma, Y; Shen, B; Li, Y; Han, G
• Is Part Of: Clinical and experimental immunology. Volume 178:Number 2(2014:Nov.)
• Page Start: 279
• Page End: 291
• Publication Date: 2014-10-01
• Subjects: macrophage -- sepsis -- T helper cell -- Tim-3; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12401
• Languages: English
• ISSNs: 0009-9104

Abstract

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 (Tim-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 Tim-3 signalling modulated the response patterns of both macrophages and T helper cells in sepsis. Blockade of the Tim-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. Tim-3 signalling was found to regulate CD80 and CD86 expression on macrophages both in vivo and in vitro . Co-culture of T cells with Tim-3 knock-down macrophages led to a biased T helper type 2 (Th2) response, partially explaining how Tim-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.