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.

Download full-text


Available from: Jessica L Palmer, Jan 06, 2014
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Both Kupffer cells and invariant natural killer T (iNKT) cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry), mRNA expression (qtPCR), nitric oxide (NO (.) ) production (Griess reaction), and protein secretion (cytometric bead-array or ELISAs) were determined. To address the potential role of NO (.) in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS) inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA)-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO (.) , and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury.
    PLoS ONE 11/2013; 8(11):e79702. DOI:10.1371/journal.pone.0079702 · 3.23 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Isolation of leukocytes from full-thickness excisional wounds has proven to be a difficult process that results in poor cell yield and holds significant limitations for functional assays. Given the increased interest in the isolation, characterization and functional measurements of wound-derived cell populations, herein we describe a method for preparing wound cell suspensions with an improved yield that enables both phenotypic and functional assessments.
    Journal of immunological methods 08/2011; 373(1-2):161-6. DOI:10.1016/j.jim.2011.08.013 · 1.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The focus of our recent work has been to complete the global high-resolution ocean and the eddy-permitting coupled ice/ocean simulations using the Los Alamos Parallel Ocean Program (POP) model and the sea ice model (CICE), as well as the first reanalysis using the Simple Ocean Data Assimilation (SODA) and POP (SODA POP 1.2). The high-resolution (0.1degree) global ocean model was run for 25 years (1979-2003) forced with synoptic atmospheric fluxes. The simulated ocean state for the post spin-up period (1994–2002) is examined in terms of its representation of the eddy variability and significant mesoscale processes by comparing energy levels and intrinsic scales with those from satellite altimetry. Also the role of the mesoscale in inter-basin property exchanges is examined with respect to the Indonesian Throughflow (ITF) and the Greenland- Iceland-Norwegian (GIN) Sea. Global coupled seaice/ ocean and stand-alone ice simulations on an eddypermitting 0.4 degree grid were run for the period 1979-2003; both were forced with synoptic atmospheric fluxes. The ice states have been compared statistically with available observations (passive microwave satellite fields, upwardlooking sonar, and ice buoys) in the latter part of the simulation. The results have lead to a suite of sensitivity runs, whose results will guide our final choices for the 0.1° global coupled sea-ice/ocean simulation. The spinup of global stand-alone 0.1 degree CICE is underway. The first reanalysis (SODA POP 1.2) using the 0.4 degree global POP and SODA is complete and is available to the general oceanographic community through Live Access Servers (LAS) at the University of Maryland and at the University of Hawaii. The reanalysis is being used to study various aspects of the global circulation including the Indonesian Throughflow, and the variability of the subtropical cells in the Pacific.
    Users Group Conference, 2005; 02/2005
Show more