Prevention of NKT Cell Activation Accelerates Cutaneous Wound Closure and Alters Local Inflammatory Signals

Department of Surgery, Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, IL, USA.
Journal of Surgical Research (Impact Factor: 1.94). 04/2010; 171(1):361-73. DOI: 10.1016/j.jss.2010.03.030
Source: PubMed


We previously reported that in the absence of NKT cells, wound closure was accelerated in a murine excisional punch wound model. Here, we explored whether purposefully inhibiting NKT cell activation had similar effects on wound closure and the dermal inflammatory response to injury. We found that prevention of NKT cell activation accelerated wound closure in a dose-responsive manner. If anti-CD1d was administered before wounding, NKT cell infiltration into cutaneous wounds was diminished without quantitative changes in cellular infiltrates. Furthermore, prevention of NKT cell activation transiently enhanced the local production of a subset of chemokines, including MIP-2, MCP-1, MIP-1α, and MIP-1β, and altered the relative expression of CD69 and CXCR2 on the surface of both circulating and wound NKT cells. Taken together, these findings suggest that wounding activates NKT cells via CD1d presentation of glycolipid antigen and help further define a role for NKT cells in the regulation of wound inflammation and closure. Many soluble factors have been targeted as potential wound healing therapies, but their clinical success has been limited. Given our findings, the NKT cell may be an attractive target for wound healing therapies.

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Available from: Jessica L Palmer, Jan 06, 2014
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    • "Other investigators reported that the accumulation of NKT cells in the liver was dependent upon LFA-1 signaling; the number of hepatic iNKT cells was reduced significantly in LFA-1-deficient mice [19]. On the other hand, CD1d (not LFA-1) expression was essential for the activation and accumulation of iNKT cells in a mouse model of wound healing [20]. To determine the contributions of LFA-1 and/or CD1d to the effect of Kupffer cells on sequestration of iNKT cells in the liver following biliary obstruction, mice were inoculated i.p. with anti-LFA-1 or anti-CD1d monoclonal antibody at 1 hour prior to BDL; control animals received normal rat IgG. "
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    • "The inflammatory cell infiltrate and its associated soluble factors are known to modulate cutaneous wound healing by promoting cell proliferation, angiogenesis and complete wound closure (Brubaker et al., 2011; Schneider et al., 2010, 2011). In efforts to better understand wound healing and the pathophysiologic conditions that can alter this process, many investigators are interested in examining the cellular subsets that reside in or infiltrate cutaneous wounds. "
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