Peptidoglycan and peptidoglycan-specific Th1 cells in psoriatic skin lesions

Abstract

We have previously demonstrated, in psoriatic skin lesions, the presence of a subset of dermal CD4+ T cells that produce interferon-gamma (IFN-gamma) in response to a mixture of cell wall proteins extracted from group A streptococci. However, the identity of the antigen(s) involved is unknown. To investigate the hypothesis that peptidoglycan (PG), the major constituent of the streptococcal cell wall, acts as a T cell activator in psoriasis, we performed in situ analysis to detect antigen-presenting cells containing PG in lesional versus non-lesional skin, and determined proliferation and IFN-gamma responses of lesional skin T cells. Increased numbers of PG-containing cells were detected in the dermal papillae and cellular infiltrates of guttate and chronic plaque skin lesions compared with normal and non-lesional psoriatic skin. A varying proportion of these were CD68+ macrophages, but the remaining cells did not double stain for either Langerhans' or dendritic cell markers. Psoriatic dermal streptococcal-specific CD4+ T cell lines proliferated and produced IFN-gamma in a self HLA-DR allele-restricted manner in response to streptococcal PG, excluding mitogenic or superantigenic stimulation, but were unresponsive to staphylococcal PG. Similarly, psoriatic staphylococcus-specific T cell lines recognized staphylococcal, but not streptococcal, PG by IFN-gamma production. The presence of PG-containing macrophages in close association with PG-specific CD4+ T cells in lesional skin suggests that PG may be responsible, at least in part, for T cell activation in psoriasis.

The association of sore throat and psoriasis might be explained by histologically distinctive tonsils and increased expression of skin-homing molecules by tonsil T cells

“…6a,b). Peptides sharing homologous sequences from streptococcal M protein and human epidermal keratins have been shown to stimulate CLA + T cells from the blood of psoriasis patients [39] and lesional T cell clones have been shown to respond in a HLA-restricted manner to streptococcal peptidoglycan [41]. We have postulated that these T cells play an important role in psoriasis [18], as improvement after tonsillectomy correlates closely with their reduction in blood [19] and T cell clones with similar TCRVB gene usage have been isolated from the tonsils and skin lesions of psoriasis patients [14].…”

New insights of T cells in the pathogenesis of psoriasis

“…28 Alternatively, they found that at least half of the streptococcal cell wall-specific Th1 cells in psoriasis lesions were specific for streptococcal peptidoglycan (PG), a major component of the Gram-positive bacterial cell wall. 29 In dermal lesions, there were observations of increased numbers of macrophages, containing streptococcal PG, within clusters of dermal T cells or in the dermal papillae. 29 It is well known that PG is a strong pro-inflammatory stimulus in chronic inflammation through its interaction with dendritic cells (DCs) and monocytes via pattern recognition receptors including Toll-like receptor 2, nucleotide-binding oligomerization domains 1 and 2 and PG recognition proteins 1-4.…”

“…29 In dermal lesions, there were observations of increased numbers of macrophages, containing streptococcal PG, within clusters of dermal T cells or in the dermal papillae. 29 It is well known that PG is a strong pro-inflammatory stimulus in chronic inflammation through its interaction with dendritic cells (DCs) and monocytes via pattern recognition receptors including Toll-like receptor 2, nucleotide-binding oligomerization domains 1 and 2 and PG recognition proteins 1-4. 30,31 Interestingly, the genes encoding the above PG recognition receptors are all located within linkage sites associated with psoriasis.…”

Bedeutung von Streptokokken für die Psoriasispathogenese

“…Mittels konfokaler Lasermikroskopie wurden Streptokokken-M-Proteine sowohl in den Papillen als auch in der Epidermis betroffener Haut nachgewiesen [51]. Weiterhin wurde berichtet, dass läsionale psoriatische Makrophagen vermehrt mit Peptidoglykan beladen sind, einem Bestandteil der Zellwand grampositiver Bakterien, und Peptidoglykan-spezifische T-Zellen zur Bildung eines T H 1-artigen Zytokinmusters anregen [3]. Mittels PCR konnte in Psoriasisläsionen Streptokokken-spezifische DNS bei solchen Patienten nachgewiesen werden, die zeitgleich eine nachweisbare Rachenkolonisierung mit S. pyogenes hatten, nicht aber bei Patienten ohne aktive Streptokokkenangina [61].…”