Increase of activated T-cells and up-regulation of Smad7 without elevation of TGF-beta expression in tonsils from patients with pustulosis palmaris et plantaris.
Pustulosis palmaris et plantaris (PPP) is known to be a skin disease related to tonsillitis, because the pustulosis often become exacerbated during acute tonsillitis and disappears after tonsillectomy. However, etiology of PPP remains unclear. In this study, we investigated the activation of tonsillar T-cell from PPP patients. Furthermore, we analyzed expressions of cytotoxic T-lymphocyte antigen-4 (CTLA4) that is a co-stimulatory molecule for inhibition of T-cell activation and of Smad7 that is a regulatory factor of TGF-beta intracellular signaling. For 47 Japanese patients with PPP who had tonsillectomy, the skin lesion was improved in 87% of PPP patient at 12 months after tonsillectomy. In quantitative immunohistologic analysis, T-cell nodules on tonsillar tissues from PPP patients were more expanded than those from the patients with obstructive sleep apnea syndrome (OSAS) (P = 0.015), and there was a positive correlation between the enlargement and clinical improvement (r = 0.422, P = 0.021). Flow cytometric analysis showed that the numbers of CD4+CD25+ and CD4+CD29+ cells in tonsils from PPP patients increased significantly compared to those from OSAS patients (P = 0.017, P = 0.016, respectively). Using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analyses with CD3+ tonsillar lymphocytes, we found that both expressions of Smad7 mRNA and protein were enhanced in PPP patients compared with OSAS patients (P = 0.03, P = 0.02, respectively), but expression of TGF-beta mRNA was not different between 2 groups. Although mRNA expression of CTLA4 was reduced in PPP patients compared with OSAS patients (P = 0.04), the CTLA4 surface protein expression was not different between 2 groups. These data suggest that helper T-cells are frequently activated in tonsils from PPP patients, and this activation may be related to unresponsiveness of TGF-beta1 by overexpression of Smad7. Such hyper-activation of T-cell may increase the risk of elicitation of self-reactive T-cell, being associated with pathogenesis of PPP.
Takahara
Miki
M
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Midorigaoka E 2-1-1-1, Asahikawa, Hokkaido 078-8510, Japan. miki.takahara@mtc.ki.se
Kishibe
Kan
K
Nozawa
Hayabusa
H
Harabuchi
Yasuaki
Y
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000276:immunology* / Q000601:surgery; D011565:Psoriasis / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D051906:Smad7 Protein; D013601:T-Lymphocytes / Q000276:immunology*; D014068:Tonsillectomy; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497806:SMAD7 protein, human; D051906:Smad7 Protein; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1