Shi Wei-min

Global Activation of CD8+ Cytotoxic T Lymphocytes Correlates with an Impairment in Regulatory T Cells in Patients with Generalized Vitiligo

Melanocyte-specific CD8+ cytotoxic T lymphocytes (CTLs) play a pivotal role in vitiligo-induced depigmentation. Yet, the mechanisms underlying the high frequency of generalized autoimmune disorders associated with generalized vitiligo (GV) are unknown. We hypothesized that an imbalance between activated CD8+ CTLs and regulatory T cells (Tregs) exists in patients with GV . Assessment of the circulating CD8+ CTLs and Tregs by flow cytometric analysis revealed an obvious expansion of CD8+ CTLs and a concomitant decrease in Treg cells in GV patients. The percentages of skin infiltrating CD8+ CTLs and Tregs were evaluated by immunohistochemistry and revealed dramatically increased numbers of both CD8+ CTLs and Tregs in the perilesional skin of GV patients. However, peripheral Tregs were impaired in their ability to suppress the proliferation and cytolytic capacity of autologous CD8+ T cells, suggesting that a functional failure of Tregs and the hyper-activation of CD8+ CTLs may contribute to progressive GV. Our data indicate that reduced numbers and impaired function of natural Tregs fail to control the widespread activation of CD8+ CTLs, which leads to the destruction of melanocytes and contributes to the elevated frequency of various associated autoimmune diseases. This knowledge furthers our understanding of the mechanisms of immune tolerance that are impaired in GV patients and may aid in the future development of effective immunotherapy for GV patients.

The effect of DNMTs and MBPs on hypomethylation in systemic lupus erythematosus

We further confirmed the increased apoptosis in the transgenic hair follicles by examining the activation status of the p38 signaling pathway, and caspase-3 activity. The p38 pathway is the primary signaling pathway leading to cell death in keratinocytes in response to ultraviolet irradiation and cytotoxic drugs [8,9]. Activation of apoptotic pathways in keratinocytes converges on activation of caspase-3, resulting in cleavage of intracellular substrates and nuclear fragmentation. A shown in Fig. 2e, a phosphorylated (activated) form of p38 and a cleaved (activated) form of caspase-3 were increased in the transgenic mouse skins at day 9, but not in the wild-type mouse skins. Thus, our results imply that PGRN overexpression induces apoptosis via caspase-3 activation through the p38 pathway. Androgenic alopecia is closely associated with increased sensitivity of hair follicles to androgens. Interestingly, PGRN mRNA is induced by steroid hormones, probably activated through atypical steroid responsive elements [1]. The inner root sheath of the bulge-isthmus portion, where apoptotic cells were intensively detected in k5-PGRN mice, is a ‘‘hot spot’’ for apoptosis in human androgenic alopecia [10]. Thus, it would be interesting to examine the relationship between PGRN and steroid hormone expression in the development of hair follicles and the progression of alopecia.

Cutaneous spindle cell squamous cell carcinoma in nevus sebaceous.

A case of a 28 year‐old Chinese male who presented with a rapidly growing tumor within a nevus sebaceous on his right cheek. The tumor was excised and immunohistochemical analysis and histology were consistent with spindle‐cell squamous cell carcinoma. To the best of our knowledge, it is the first report of cutaneous spindle‐cell squamous cell carcinoma developing in nevus sebaceous in the English literature. This report highlights the importance of early excision of any nevus sebaceous with a history of change.