Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions

Abstract

In psoriasis, leukocytes that infiltrate skin lesions have been shown to be involved in the pathogenesis of this disease. Previous investigations reporting the presence of CXCR3(+) T lymphocytes in psoriatic lesional skin have suggested a role of this receptor in the recruitment of T cells into the lesion. The purpose of this study was to quantify the mRNA levels of CXCR3 and to perform a systematic analysis of the cell populations that express CXCR3 in human lesional and non-lesional psoriatic biopsies. We showed by real-time reverse transcriptase-polymerase chain reaction that the mRNA levels of CXCR3 and its ligands, CXCL9-11, were significantly elevated in psoriatic lesions, as compared to non-lesional samples. Serial cryostat sections of psoriasis skin biopsies were evaluated by immunohistochemistry. The number of CXCR3(+) cells was low in non-lesional tissues. Quantitative image analysis demonstrated significant increases in the number of both epidermal and dermal CXCR3(+) cells in lesional compared with non-lesional biopsies. The majority of CXCR3(+) cells were located in the dermis of the lesional skin and 74% were demonstrated to be CD3(+) T lymphocytes. A small number of CXCR3(+) cells were CD68(+) myeloid cells. In addition, we found that nearly all BDCA-2(+) plasmacytoid dendritic cells in the psoriatic biopsies were CXCR3(+). These findings support and extend prior reports suggesting the potential role for CXCR3 in the pathophysiology of plaque psoriasis, by mediating the recruitment of plasmacytoid dendritic cells and T cells into the developing lesions.

The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis

“…The role of T-cell-derived IFN-g in psoriasis, a disease with an IFN-g-genomic signature 55 , should not be underscored. IFN-g activates keratinocytes, induces inflammatory chemokines/ cytokines 31,[56][57][58] and produces histological features of psoriatic lesions when injected in non-lesional psoriasis skin 59 . Indeed, a recent mouse model of psoriatic skin inflammation showed CD8 þ T cells being critical players via IFN-g secretion 60 .…”

Psoriasis, a Systemic Disease Beyond the Skin, as Evidenced by Psoriatic Arthritis and Many Comorbities – Clinical Remission with a Leishmania Amastigotes Vaccine, a Serendipity Finding

“…The majority of CXCR3+ cells were located in the dermis of the lesional skin and 74% were CD3+ T lymphocytes. A small number of CXCR3+ cells were CD68+ myeloid cells and all BDCA-2+ plasmacytoid dendritic cells were CXCR3+ (Chen et al, 2010).…”

Psoriasis: Epidemiology, Clinical and Histological Features, Triggering Factors, Assessment of Severity and Psychosocial Aspects

“…The primary immune defect appears to be an increase in cell signalling via chemokines and cytokines that act upregulating gene expression, causing keratinocyte hyperproliferation. T lymphocytes and their cytokines and chemokines appear to be the driver of lesion development and persistence, although other cells, such as endothelial cells, dendritic cells, neutrophils and www.intechopen.com keratinocytes play also an important role, along with other cytokines and growth factors (Chen, de Groot et al;Wollenberg, Wagner et al 2002;Sano, Chan et al 2005). Currently, it is proposed that psoriasis development depends on skin infiltration of T helper (Th)1/Th17 cells that stimulate macrophages and dermal dendritic cells to release mediators that sustain inflammation and cause abnormal keratinocyte proliferation.…”