Abstract
The MHC class I-like protein CD1d is a nonpolymorphic molecule that plays a central role in development and activation of a subset of T cells that coexpress receptors used by NK cells (NK-T cells). Recently, T cells bearing NK receptors were identified in acute and chronic lesions of psoriasis. To determine whether NK-T cells could interact with epidermal cells, we examined the pattern of expression of CD1d in normal skin, psoriasis, and related skin disorders, using a panel of CD1d-specific mAbs. CD1d was expressed by keratinocytes in normal skin, although expression was at a relatively low level and was generally confined to upper level keratinocytes immediately beneath the lipid-rich stratum corneum. In contrast, there was overexpression of CD1d in chronic, active psoriatic plaques. CD1d could be rapidly induced on keratinocytes in normal skin by physical trauma that disrupted barrier function or by application of a potent contact-sensitizing agent. Keratinocytes displayed enhanced CD1d following exposure to IFN-gamma. Combining CD1d-positive keratinocytes with human NK-T cell clones resulted in clustering of NK-T cells, and while no significant proliferation ensued, NK-T cells became activated to produce large amounts of IFN-gamma. We conclude that CD1d can be expressed in a functionally active form by keratinocytes and is up-regulated in psoriasis and other inflammatory dermatoses. The ability of IFN-gamma to enhance keratinocyte CD1d expression and the subsequent ability of CD1d-positive keratinocytes to activate NK-T cells to produce IFN-gamma, could provide a mechanism that contributes to the pathogenesis of psoriasis and other skin disorders.
Highlights
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Keratinocytes in vitro and in vivo synthesized and expressed CD1d, which was capable of triggering CD161ϩ NK-T cells to produce high levels of IFN-␥, but not IL-4
We observed that cross-linking the TCR in these NK-T cell clones led to enhancement of both IFN-␥ and IL-4 levels [29], suggesting that a selective stimulatory event was being mediated by CD1d-expressing keratinocytes, leading to preferential IFN-␥ production
Summary
NKR, NK cell receptor; NN skin, normal skin; PN skin, symptomless skin from patients with psoriasis elsewhere; PP skin, active untreated psoriatic plaques; DN, double negative; TPA, 12-O-tetradecanoyl phorbol-13acetate; TBS, Tris-buffered saline, pH 7.6; PNGase F, peptide N-glycosidase F. CD1d in psoriasis and other skin disorders, we searched for NK-T cells bearing V␣24 and V11 as well as CD94 and CD161. This report documents patterns of CD1d expression by keratinocytes in vitro and in human skin and psoriasis in vivo. We observed in psoriatic lesions the presence of intraepidermal lymphocytes expressing a variety of markers shared by classical NK-T cells. To explore the functional significance of these in vivo findings, NK-T cell clones were used to explore the potential for CD1d expressed on keratinocytes to trigger CD1d mediated immunologic responses
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