Up-regulation of CC chemokine receptor 6 on tonsillar T cells and its induction byin vitrostimulation withα-streptococciin patients with pustulosis palmaris et plantaris

Abstract

SummaryPustulosis palmaris et plantaris (PPP) is a tonsil-related disease; tonsillectomy is somewhat effective in treating the condition. However, the aetiological association between the tonsils and PPP has not yet been elucidated fully. Recently, some chemokines and chemokine receptors, including CC chemokine receptor (CCR) 4, CCR6 and CX chemokine receptor (CXCR) 3, have been reported to play important roles in the development of psoriasis, a disease related closely to PPP. In this study, we found that CCR6 expression on both tonsillar and peripheral blood T cells was up-regulated more intensively in PPP patients than in non-PPP patients (P < 0·001 for both), but CCR4 and CXCR3 expressions were not. In vitro stimulation with a-streptococcal antigen enhanced CCR6 expression significantly on tonsillar T cells in PPP patients (P < 0·05), but this was not observed in non-PPP patients. The chemotactic response of tonsillar T cells to the CCR6 ligand CC chemokine ligand (CCL) 20 was significantly higher in PPP patients than in non-PPP patients (P < 0·05). The percentage of CCR6-positive peripheral blood T cells decreased after tonsillectomy in PPP patients (P < 0·01); this decrease correlated with an improvement of skin lesions (P < 0·05, r = -0·63). The numbers of CCR6-positive cells and the expression of CCL20 were increased significantly in pathological lesions compared with non-pathological lesions in PPP skin (P < 0·01, P < 0·05 respectively). These results suggest that a novel immune response to a-streptococci may enhance CCR6 expression on T cells in tonsils and that CCR6-positive T cells may move to peripheral blood circulation, resulting in recruitment to target skin lesions expressing CCL20 in PPP patients. This may be one of the key roles in pathogenesis of the tonsilrelated disease PPP.

Pustulosis palmoplantaris is a disease distinct from psoriasis

“…The activation of T cells via inducible co-stimulator (ICOS) in focal infection likely triggers the skin inflammation associated with PPP (20). Furthermore, CCR6 expression on tonsillar and peripheral blood T cells was upregulated in PPP patients (21).…”

Tonsillectomy as a treatment for psoriasis: A review

“…They also showed that in PPP patients CCR6 expression on tonsillar T cells was significantly enhanced after in-vitro stimulation with alpha-streptococcal antigen (P < 0.05), but this was not observed in non-PPP patients. These results suggest that an immune response to alpha-streptococci may enhance CCR6 expression on T cells in tonsils and that CCR6-positive T cells may move to the peripheral blood circulation, resulting in recruitment to target skin lesions in PPP patients (14). While there are many proposed pathways and factors in the theory behind how tonsillectomies may affect PPP, the complete pathophysiology is still not well understood and further research is still needed.…”

“…This patient cohort was enriched for cases in which tonsillitis may have served as a trigger of skin disease, as 9 of the 14 patients reported multiple episodes of acute tonsillitis and 8 of these patients had exacerbations of psoriasis during tonsillitis episodes. Twelve of the 14 patients reported an effective to complete response to tonsillectomy, two patients reported a partial response, and zero patients reported no response (14). The therapeutic effect of tonsillectomy has also been examined in generalized pustular psoriasis (GPP), which shares clinical and histologic features with PPP.…”

Triggering Role of Focal Infection in the Induction of Extra-Palmoplantar Lesions and Pustulotic Arthro-Osteitis Associated with Palmoplantar Pustulosis

“…These data suggest that activated tonsillar T cells by infection migrate into the skin forming cutaneous lesions in PPP via a number of inflammatory cytokines. C-C chemokine receptor, CCR6, expression on both tonsilar and peripheral blood T cells was upregulated in patients with PPP [10]. In vitro stimulation with α-streptococcal antigen significantly enhanced CCR6 expression on tonsillar T cells in patients with PPP [10].…”

“…C-C chemokine receptor, CCR6, expression on both tonsilar and peripheral blood T cells was upregulated in patients with PPP [10]. In vitro stimulation with α-streptococcal antigen significantly enhanced CCR6 expression on tonsillar T cells in patients with PPP [10]. Further, bacterial products stimulate the enhanced production of IL-23, which triggers T cells to produce IL-17.…”