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Am J Respir Cell Mol Biol. 2016 Aug;55(2):264-74. doi: 10.1165/rcmb.2015-0380OC.

Thymic Stromal Lymphopoietin Improves Survival and Reduces Inflammation in Sepsis.

Author information

1
1 Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington.
2
2 Departments of Pediatrics and.
3
3 Pathology, University of Washington School of Medicine, Seattle, Washington.
4
4 Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington; and.
5
5 Department of Immunology, University of Washington School of Medicine, Seattle, Washington.

Abstract

The mechanisms that contribute to homeostasis of the immune system in sepsis are largely unknown. One study suggests a potential detrimental role for thymic stromal lymphopoietin (TSLP) in sepsis; however, the immune-regulatory effects of TSLP on myeloid cells within the intestinal microenvironment suggest the contrary. Our objective was to clarify TSLP's role in sepsis. Cecal ligation and puncture was performed in mice with total or myeloid-specific deficiency in the TSLP receptor (TSLPR). Survival was monitored closely, peritoneal fluids and plasma were analyzed for markers of inflammation, and myeloid cell numbers and their ability to produce inflammatory mediators was determined. The interaction of TSLP with TSLPR in myeloid cells contributed to mouse survival after septic peritonitis. Mice with TSLPR deficiency in myeloid cells displayed excessive local and systemic inflammation levels (e.g., increased inflammatory cell and cytokine levels) relative to control mice. Moreover, hepatic injury was exacerbated in mice with TSLPR deficiency in their myeloid cells. However, the enhanced inflammatory response did not affect the ability of these mice to clear bacteria. Resident neutrophils and macrophages from septic mice with TSLPR deficiency exhibited an increased ability to produce proinflammatory cytokines. Collectively, our findings suggest that the effects of TSLP on myeloid cells are crucial in reducing the multiple organ failure that is associated with systemic inflammation, which highlights the significance of this cytokine in modulating the host response to infection and in reducing the risks of sepsis development.

KEYWORDS:

inflammation; myeloid cells; sepsis; thymic stromal lymphopoietin

PMID:
26934097
PMCID:
PMC4979369
DOI:
10.1165/rcmb.2015-0380OC
[Indexed for MEDLINE]
Free PMC Article

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