Altered keratin 17 peptide ligands inhibit in vitro proliferation of keratinocytes and T cells isolated from patients with psoriasis

Predominance of activated, clonally expanded T helper type 17 cells within the CD4+ T cell population in psoriatic lesions

“…There may be therapeutic advantage in boosting local IL-10 responses, as production of the cytokine has been implicated previously in the inhibition of psoriatic keratinocyte and T cell proliferation [37].…”

Psoriasis – as an autoimmune disease caused by molecular mimicry

“…Moreover, these altered peptide ligands induced production of IL-4, and the anti-inflammatory cytokines IL-10 and TGF-b and, furthermore, supernatants from the T cell cultures inhibited keratinocyte proliferation in vitro [49].…”

“…More recently, it was reported that it was possible to abolish the T cell proliferation and IFN-g production, induced by these peptides, by single alanine residue substitutions at a critical TCR contact position [49]. Moreover, these altered peptide ligands induced production of IL-4, and the anti-inflammatory cytokines IL-10 and TGF-b and, furthermore, supernatants from the T cell cultures inhibited keratinocyte proliferation in vitro [49].…”

“…12 and here, Figure 3, step 1) NB Macrophages are not found in efferent lymph nor have they been observed to migrate from (lymphoid) tissues into the circulation. 7) Increased frequency in the blood of psoriasis patients of both CD4 + and CD8 + T cells that respond to antigen determinants that are common to streptococcal M-protein and type 1 keratins [43,44,[47][48][49] (Figure 3, step 2). 8) Re-circulating CLA + effector CD4 + T cells migrate mainly into lesional dermis but CLA + effector CD8 + T cells migrate mostly through the dermis and into the epidermis [5,6] (Figure 3, steps 3 and 4).…”

Keratin 17 as a therapeutic target for the treatment of psoriasis

“…In autoimmune disease, it was reported that altered peptide ligands can abolish the T cell proliferation and IFN-g production although the biochemical and cellular mechanisms underlying the T-cell responses to altered peptide ligands are not completely understood. We produced several psoriatic altered peptide ligands by single alanine residue substitutions and found that the altered peptide ligands 119R and 355L can down-regulate the proliferation of psoriatic T cells effectively [33]. Moreover, altered peptide ligands 119R and 355L significantly inhibit the secretion of IFN-g and IL-2 in parallel to the up-regulation of IL-4,IL-10, and TGF-b, indicating that the altered peptide ligands have a potent immunomodulatory role.…”