T lymphocytes derived from skin lesions of patients with psoriasis vulgaris express a novel cytokine pattern that is distinct from that of T helper type 1 and T helper type 2 cells

Abstract

In various immunological disorders the pathomechanisms of tissue damage are causally associated with specific patterns of locally produced cytokines. To study the molecular and cellular mechanisms involved in the manifestation of psoriasis vulgaris we have assessed the cytokine mRNA profile expressed in lesional psoriatic skin and in T cell clones (TCC) that were established from skin lesions of patients with psoriasis. As demonstrated by use of the polymerase chain reaction (PCR), psoriasis lesions consistently exhibit transcription of a complex pattern of cytokines. It includes mediators selectively produced by T lymphocytes [interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, interleukin (IL)-2, IL-3 and IL-5] as well as cytokines secreted by various cell types [transforming growth factor (TGF)-alpha/-beta, TNF-alpha, IL-6/-8 and granulocyte-macrophage-colony stimulating factor], while IL-4 is missing. With the exception of TGF-alpha, this cytokine profile was also observed in lesional psoriatic T cell clones yielding supernatants mitogenic for keratinocytes in vitro (MTCC), but not in T cell clones yielding supernatants that inhibited keratinocyte proliferation (STCC). The congruent cytokine expression of psoriatic skin lesions and MTCC emphasizes that inflammation in psoriasis is driven by a sofar unrecognized regulatory T cell subset that may serve to control epidermal regeneration and convey immunosurveillance over epithelial surfaces. It is characterized by the combined expression of IFN-gamma, TGF-beta, IL-2 and IL-5 in the absence of IL-4 and by its selective capacity to enhance keratinocyte proliferation. This newly defined combination of regulatory properties of a distinct T cell population cannot be reconciled with an immune response of the T helper cells (TH)0, TH1 or TH2 type.

Up-regulation of Id1 in peripheral blood of psoriatic patients

“…It has been shown using a T-cell line model that Id1 expression stimulates baseline levels of NF-κB activity and further enhances NF-κB activation upon T-cell receptor signaling, and that Id1-potentiated activation of NF-κB leads to overproduction of cytokines such as TNF-α and interferon gamma (IFN-γ) in a T-cell line as well as in thymocytes (Yang et al, 2006). Since it has been well documented that an increase in cytokine levels produced by Th1 cells, including TNF-α and IFN-γ, is observed in lesional T lymphocytes and circulating T lymphocytes of patients with psoriasis (Ettehadi et al, 1994;Bonifati et al, 1994;Prinz et al, 1994;Vollmer et al, 1994;Bata-Csorgo et al, 1995a,b;Szabo et al, 1998;Austin et al, 1999;Friedrich et al, 2000), the overexpression of these cytokines may occur as a result of Id1-potentiated activation of NF-κB. Interestingly, a recent genome-wide scan further emphasized the role of the NF-κB pathway in psoriasis (Nair et al, 2009).…”

Ezrin, Maspin, Peroxiredoxin 2, and Heat Shock Protein 27: Potential Targets of a Streptococcal-Induced Autoimmune Response in Psoriasis

“…Preparation and cultivation of PBMCs, T cell stimulation, and generation of Ag-specific T cell lines were done as described (25,26). For T cell stimulation, 1 3 10 6 /ml PBLs were grown in the presence of protein Ags (5 mg/ml), peptides (10 mg/ml), or PHA (1:100) for 40 h (IFN-g-release ELISPOT) or 5 d ([ 3 H]thymidine incorporation).…”

Genes and structure of selected cytokines involved in pathogenesis of psoriasis.

“…Psoriatic plaques demonstrate predominance of Th1-type cytokines such as IL-2 and IFN-γ [72,73]. However, different research groups revealed other cytokines involvement, which cannot be simply classified as Th1, Th0 or Th2 type, in psoriasis development [74,75].…”