Article

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: 2.12). 04/2010; 171(1):361-73. DOI: 10.1016/j.jss.2010.03.030
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
92 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There have been extensive studies regarding which types of T lymphocytes are involved in psoriasis vulgaris (PV). However, it has remained unclear as to which types of T lymphocytes may directly contribute to psoriasiform epidermal and vascular hyperplasia. To understand the role of TCRVα24+ invariant natural killer T (iNKT) in the development of PV, a total of 17 patients with were enrolled in this study. In the present study, using biopsy samples of PV plaques, TCRVα24(+) invariant natural killer T (iNKT) cells were investigated regarding cytokine production to understand their roles in development of disease. The number of IFN-γ+ iNKT cells correlated with the length of the psoriasiform hyperplasia rete ridge and the psoriasis area and severity index (PASI). IFN-γ+ iNKT cells in psoriatic skin exhibited higher C-C chemokine receptor type 5 (CCR5) expression, and the amount of C-C chemokine ligand 5 (CCL5), a ligand for CCR5, was increased in capillary veins of psoriasis plaques. CCR5+ iNKT cell numbers significantly correlated with the number of capillary vein endothelial cells expressing CCL5 in PV. Furthermore, the number of CCL5+ capillary veins correlated with the maximal rete ridge length. IFN-γ/CCR5 expression in iNKT cells and CCL5 expression in dermal papillae vessels of dermal papillae are correlated with the development of psoriasiform hyperplasia and microabscess. We propose that these iNKT cells may become useful targets for development of novel therapeutic approaches to PV. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 05/2014; 170(5):1048-1055. DOI:10.1111/bjd.12812 · 4.10 Impact Factor
  • Source
    [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 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study tested the hypothesis that heightened bacterial colonization and delayed wound closure in aged mice could be attenuated by granulocyte-colony stimulating factor (G-CSF) treatment. Previously, we reported that aged mice had elevated bacterial levels, protracted wound closure and reduced wound neutrophil accumulation following Staphylococcus aureus wound infection relative to young mice. In aseptic wound models, G-CSF treatment improved wound closure in aged mice to rates observed in young mice. Given these data, our objective was to determine if G-CSF could restore age-associated differences in wound bacterial burden and closure by increasing wound neutrophil recruitment. Young (3-4 month) and aged (18-20 month) BALB/c mice received three dorsal, subcutaneous injections of G-CSF (250 ng/50 μl/injection) or saline control (50 μl/injection) 30 minutes after wound infection. Mice were sacrificed at days 3 and 7 post wound infection and bacterial colonization, wound size, wound leukocyte accumulation and peripheral blood were evaluated. At days 3 and 7 after wound infection, bacterial colonization was significantly reduced in G-CSF-treated aged mice to levels observed in saline-treated young animals. Wound size was reduced in G-CSF-treated aged animals, with no affect on wound size in G-CSF-treated young mice. Local G-CSF treatment significantly enhanced neutrophil wound accumulation in aged mice, whereas there was no G-CSF-induced change in young mice. These data demonstrate that G-CSF enhances bacterial clearance and wound closure in an age-dependent manner. Moreover, G-CSF may be of therapeutic potential in the setting of post-operative wound infection or chronic, non-healing wounds in elderly patients.
    Shock (Augusta, Ga.) 07/2013; DOI:10.1097/SHK.0b013e3182a43651 · 2.73 Impact Factor

Full-text (2 Sources)

Download
40 Downloads
Available from
May 29, 2014