Expression of Thymic Stromal Lymphopoietin in Immune-Related Dermatoses.

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

Efficacy and safety of tetracyclines for pemphigoid: a systematic review and meta-analysis.

The aim of this review was to evaluate the efficacy and safety of tetracyclines for treatment of pemphigoid. We searched PubMed, EMBASE, Ovid, Web of Science, and the Cochrane Library for studies involving pemphigoid patients treated with tetracyclines published in English before 29 February 2020. References of included studies were also screened to widen the scope of the literature search. Data regarding predefined clinical outcomes of 341 patients from 77 studies were extracted and analyzed. A meta-analysis was conducted on the basis of 4 studies including 2 randomized controlled trials and 2 comparative studies. The patients had a mean age of 74.60 ± 13.18 years, 45.4% were males, and 54.6% were females. There were 185 patients with mild-to-moderate and 143 patients with severe disease. The average initial doses were 1.62 ± 0.39 g/day for tetracycline, 0.20 ± 0.01 g/day for doxycycline, and 0.11 ± 0.05 g/day for minocycline. The average time on tetracyclines was 3.74 ± 5.99 months, and 261 (81.3%) patients reported partial or complete remission. Relapses occurred in 72 (28.3%) cases. Adverse effects were experienced by 130 (41.9%) patients. The pooled ORs for short-term effectiveness, relapse, adverse effects, and 1-year survival in patients treated with oral tetracyclines vs. systemic corticosteroids were 0.40 (95% CI, 0.22-0.76), 0.69 (95% CI, 0.44-1.10), 0.47 (95% CI, 0.27-0.82) and 2.02 (95% CI, 1.16-3.50), respectively. Compared to doxycycline and minocycline, tetracycline was significantly associated with better treatment outcomes and fewer adverse effects (p < 0.05). This review revealed tetracyclines' efficacy and safety in pemphigoid treatment and may offer support for clinical use of tetracyclines in pemphigoid.

Thymic Stromal Lymphopoietin Is Implicated in the Pathogenesis of Bullous Pemphigoid by Dendritic Cells.

OBJECTIVES: Both thymic stromal lymphopoietin (TSLP) and dendritic cells (DCs) are involved in many autoimmune diseases, but the potential roles of TSLP and DCs in bullous pemphigoid (BP) have not been clarified. We sought to explore the contributions of TSLP and DCs in patients with BP. METHODS: TSLP levels in sera and blister fluids were measured by enzyme-linked immunosorbent assay. The TSLP expression in the BP lesional skin was detected by immunohistochemical staining. Infiltration of DCs, marked by DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and its relationship with TSLP and TSLP receptors was evaluated by immunofluorescence staining. RESULTS: We found that TSLP levels in sera and in blister fluids of patients with BP were higher compared to the control groups. In patients with BP, TSLP levels in sera correlated with TSLP levels in blisters. The expression of TSLP in the BP lesional skin was higher compared to the healthy controls' skin. Greater numbers of TSLP-positive cells were observed in the epidermis of patients with BP compared to the healthy controls. Greater numbers of DC-SIGN-positive cells were present in the BP lesional skin compared to the skin of controls. The expression of TSLP was highly upregulated in DC-SIGN-positive cells, and most DC-SIGN-positive cells expressed TSLP receptors. CONCLUSIONS: We conclude that TSLP may activate DC-SIGN-positive DCs directly, which may be involved in the pathogenesis of BP.

Treatment of bullous pemphigoid in Chinese patients with Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) is a traditional Chinese herb used in many medicinal applications, but the treatment of bullous pemphigoid (BP) with TwHF has never been reported. The aim of this study was to evaluate the efficacy and safety of TwHF in BP patients. A retrospective study was performed from January 2015 to September 2019 in the Department of Dermatology, Peking Union Medical College Hospital. A total of 10 patients with mild to moderate BP and treated with TwHF were enrolled in the study with 10 mild or moderate BP patients treated with systemic glucocorticoid randomly selected as controls. In the TwHF group, a major response was seen in seven patients, a minor response in one and no response was seen in two patients. In the glucocorticoid group, a major response was seen in nine patients and a minor response in one patient. Two patients experienced treatment failure. The time to disease control in the TwHF group (34 ± 11 days) was longer as compared to the glucocorticoid group (18 ± 8 days, P < .05). Ten patients relapsed during the follow-up period. The adverse events in the TwHF group were lower than those in the glucocorticoid group (13 vs 19). Low-dose TwHF may be effective and safe for treating mild and moderate BP.

Msi1 promotes tumor progression by epithelial-to-mesenchymal transition in cervical cancer.

Musashi1 (Msi1) is an RNA-binding protein that has been reported to be a pivotal regulator in tumorigenesis and progression in several cancers. However, its function and mechanism in cervical cancer is still unknown. In this study, Msi1 expression was found elevated in cervical cancers by immunohistochemistry and correlated with poor outcomes. Then, endogenous Msi1 was silenced in cervical cancer cell lines by short hairpin RNA, and its function and mechanism were determined. The results showed that the silencing of Msi1 in SiHa and HeLa cells inhibited the cells' migratory and invasive abilities in vitro and tumor progression in vivo. Epithelial-to-mesenchymal transition (EMT) markers were down-regulated, and Wnt activity was inhibited by the silencing of Msi1. In clinical tissues, positive correlations between Msi1 and EMT markers were found. In conclusion, Msi1, a diagnostic marker and potential therapeutic target, promoted the EMT progression through activation of the Wnt signaling pathway in cervical cancers, thereby contributing to poor prognosis.