Intralesional immunotherapy for non-genital warts: A systematic review and meta-analysis.

Background Intralesional immunotherapy has been reported to be effective for warts and to show good safety profiles, but this has not yet been systematically studied. Aims To determine the efficacy and safety of intralesional immunotherapy for treating non-genital warts. Methods We comprehensively searched the MEDLINE, Embase, Web of Science and Cochrane Library databases from the times of their inception to January 3, 2020. The primary outcome was the rate of complete response of all lesions. The distant complete response rate of warts located in an anatomically different body part and the recurrence rate were also analyzed. Results A total of 54 prospective studies was ultimately included. The immunotherapeutic agents used were Mycobacterium w vaccine, measles, mumps and rubella vaccine, purified protein derivative, Candida antigen, interferon, bacillus Calmette-Guérin vaccine and others. The pooled rate of complete response among all patients with non-genital warts treated using intralesional immunotherapy was 60.6% (95% confidence interval 54.8-66.5%). The pooled recurrence rate was 2.0% (95% confidence interval, 1.1-2.9%). All reported adverse events were mild and transient. Limitations The heterogeneity among studies Conclusion Intralesional immunotherapy is suggested for use in patients with multiple warts, given its promising results, good safety profile and low recurrence rate.

Preventive Effects of a Human Hematopoietic Mesenchymal Stem Cell (hHMSC) Therapy in Ovalbumin-Induced Food Allergy.

No effective therapeutic strategies have been developed against food allergies. Immunomodulation during early infant period could prevent the development of food allergies. We investigated the preventive effects of human hematopoietic mesenchymal stem cells (hHMSCs) in mice with ovalbumin (OVA)-induced food allergy. BALB/c mice with OVA-induced food allergy were divided into 3 groups, and each group was treated with hHMSCs or hHMSC culture medium (hHMSC-CM) or saline. Ear thickness, allergy score, rectal temperature, and diarrhea occurrence were checked. Total IgE, OVA-specific IgE, and mucosal mast cell protease-1 (mMCP-1) were measured by ELISA. Other allergic parameters were analyzed using histology specimens, RT-PCR, and flow cytometry. Treatment with hHMSCs or hHMSC-CM significantly suppressed the frequency of anaphylactic response and rectal temperature decline, reduced diarrhea, total IgE, OVA-specific IgE, and mMCP-1. While the treatment decreased the level of Th2 cytokines, it enhanced IL-10 and TGF-ß1 mRNA. Exposure to hHMSC or hHMSC-CM did not generate regulatory T cells, but reduced mast cells. The immunomodulatory effect on the Th2 cytokines was greater in hHMSC-CM than in hHMSCs. hHMSC treatment may be a promising preventive intervention against food allergy. Further studies are needed to elucidate the key substances released from hHMSC to induce immune tolerance.

Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/ß-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles.

Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/ß-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression-including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1ß, and IL-15-and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/ß-catenin signaling pathway, such as in the Wnt families, ß-catenin, phosphorylated GSK-3ß and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/ß-catenin and JAK/STAT pathways in hORSCs.

Inflammasome-mediated Inflammation by Malassezia in human keratinocytes: A comparative analysis with different strains.

Malassezia species are associated with several common dermatologic conditions including pityriasis versicolor, seborrhoeic dermatitis, folliculitis, and atopic dermatitis and dandruff. However, its causal role remains to be established. We intended to explore the role of inflammasome activation in human keratinocytes in response to three different Malassezia species. We compared the different activation patterns of inflammasomes and the expression of pro-inflammatory cytokines and antimicrobial peptides by three different Malassezia species-M. restricta, M. globosa and M. sympodialis-in human keratinocytes. We found that different Malassezia species, especially M. restricta and M. globosa could induce nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin-domain-containing protein (NLRP)3-apoptosis-associated speck-like protein containing CARD (ASC) inflammasome activation and subsequent interleukin (IL)-1ß secretion in human keratinocytes. Malassezia species variably induced thymic stromal lymphopoietin, ß-defensin 2, and LL-37. IL-8 mRNA and IL-22 protein significantly increased in the M. sympodialis-treated group, and Chemokine C-C motif ligand (CCL)17 and CCL22 mRNA were increased in response to M. globosa- and M. restricta- treated keratinocytes, respectively. Our data show that various species of Malassezia promote variable inflammatory responses in keratinocytes by activating NLRP3 inflammasomes, pro-inflammatory cytokines and chemokines, and antimicrobial peptides.

The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells.

Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/ß-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/ß-catenin signaling pathway, including Lef1 and ß-catenin, and suppressed the transcription of DKK1 in hDPCs, but not its translation. Ruxolitinib reverted IFN-γ-induced expression of caspase-1, IL-1ß, IL-15, and IL-18, and stimulated several growth factors, such as FGF7. Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-γ pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-γ-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/ß-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-γ-induced collapse of hair-follicle immune privilege.