Palmoplantar pustulosis (PPP) is an autoimmune disease characterized by psoriasis-like erythematous lesions on palms and/or soles due to an abnormal humoral immune response. Tonsillectomy is effectively employed for the treatment of PPP; however, how tonsils are involved in the aetiology of PPP remains unclear. Here we analysed surgically resected palatine tonsils from 36 cases of PPP as well as usual recurrent tonsillitis (RT) as a control. Histological examination revealed that a unique lesion, with lymphoid follicles surrounded by reticular crypt epithelial cells, was more frequently observed in tonsils of patients with PPP than in those with RT (p < 0.0001; PPP vs RT). Interestingly, crypt epithelial cells in primary cultures derived from PPP tonsils showed marked production of interleukin-6 (IL-6). Moreover, these epithelial cells from PPP tonsils expressed p53-related transcription factors in their nuclei that were found to contribute to the up-regulation of IL-6 gene expression. These findings suggest that, at least in part, the specialized lymphoepithelial symbiosis of PPP tonsils, under the control of p53-related factors, may be relevant to the generation of the impaired micro-environment underlying the aberrant production of autoantibodies.

In this study, we report the unique role of arachidonate 5-lipoxygenase (Alox5) in the regulation of specific humoral immune responses. We previously reported an L22 monoclonal antibody with which human primary resting B cells in the mantle zones of lymphoid follicles are well-defined. Proteomics analyses enabled identification of an L22 antigen as Alox5, which was highly expressed by naive and memory B cells surrounding germinal centers. Cellular growth of mantle cell lymphoma cells also seemed to depend on Alox5. Alox5

In this study, we investigated the localization and functional significance of p53 tumor suppressor-like molecules, p63 and p73, in human thymic epithelial cells (TECs). Immunohistochemical studies showed particular distribution profiles of p63 and p73 in thymic epithelium, in which cortical TECs preferentially expressed p63 in their nuclei whereas subcapsular and medullary TECs expressed both p63 and p73 in their nuclei. The wide distribution of p63 in TECs was further suggested by studies using TECs of primary culture. In vitro studies using two human TEC lines demonstrated that p63 was capable of up-regulating intercellular adhesion molecule-1 (ICAM-1) and enhancing the production of IL-6 and IL-8. Moreover, in vitro studies also indicated that p73, but not p63, had the capacity to induce granulocyte macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) in the TEC lines. These findings suggest that p63 would regulate the cell adhesive property through ICAM-1/LFA-1 interaction and the production of IL-6 and IL-8, probably in all TEC subtypes. p73 in subcapslar and medullary TECs was suggested to play a role in the regulation of the production of GM-CSF and G-CSF, which might stimulate other stromal cells such as dendritic cells, macrophages and endothelial cells around these regions.

Abstract:The nature of the target molecule of TCR␥␦ T cell-mediated lysis remains to be determined. As we previously reported, #067 monoclonal antibody (mAb) recognizes one of the transformation-associated antigens, designated as #067 antigen. This antigen is expressed on the cell surface of rat fibrosarcoma W31 cells, which are established by transformation of fetal fibroblastic WFB cells with H-ras oncogene. It has been suggested that the #067 antigen is a target molecule for TCR␥␦ T cells since #067 mAb inhibited TCR␥␦ T cell-mediated lysis against #067 positive cells. In this study we attempted to identify the protein sequence of the #067 antigen. By using molecular cloning techniques, we demonstrated that a calcium binding protein, S100A4, was possibly one and the same molecule as the #067 antigen. It was shown that the expression of S100A4 was higher in W31 cells than in WFB cells at transcription and protein level. Flow cytometry and immunocytochemical studies showed that #067 antigen partially co-localized with S100A4 on the cell surface as well as the cytoplasm of W31 cells. Moreover, rabbit anti-S100A4 polyclonal antibodies (pAb) inhibited TCR␥␦ T cell-mediated lysis against #067 positive cells. Our results indicated that S100A4 may play a role as a possible target molecule for TCR␥␦ T cell-mediated lysis although how S100A4 is involved in TCR␥␦ T cell-mediated lysis remains to be determined.

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