rHu MIP-4
- Known as:
- rHu MIP-4
- Catalog number:
- AK8218-0002
- Product Quantity:
- 2
- Category:
- -
- Supplier:
- Akro
- Gene target:
- rHu MIP-4
Related products to: rHu MIP-4
Related articles to: rHu MIP-4
- Netherton syndrome (NS) is a rare ichthyosis caused by SPINK5-null mutations, resulting in erythroderma, ichthyosis linearis circumflexa, and atopic diathesis. Elevated serum IgE levels and activation of the KLK5-PAR2-TSLP axis suggest involvement of Th2-skewed immunity in NS. In this pilot study, we investigated the effects of IL-4/IL-13 blocking with dupilumab on NS features. At baseline, Th2-chemokines CCL11, CCL17, CCL18, CCL26, and serum IgE were more elevated in atopic dermatitis (AD) than in NS vs. controls (ctrls). AD exhibited elevated serum levels of CCL27, LDH, and eosinophils, while NS showed higher levels of IL-9 and IL-18. Epidermal aberrations, including acanthosis and SC-detachment, were present in NS versus ctrls. The number of CD3+ T cells increased, while CD1a + Langerhans cell numbers decreased in NS skin. Amounts of KLK5 were reduced, and the distribution of KLK7 was abnormal in NS epidermis as compared to ctrls. Reduced amounts of FLG, CDSN, and DSG1 highlight impaired keratinocyte late differentiation in NS. Amounts of epidermal TSLP were diminished. Upon dupilumab treatment, clinical improvement in NS began as early as week 8 and continued up to 30 months, with no serious side effects reported. Serum levels of IgE, CCL17, CCL26, IFN-γ and IL-18 decreased upon IL-4/IL-13 blockade, and alterations of cutaneous immune cells improved in NS. Furthermore, the epidermal protease inhibitor WFDC12 expression increased after dupilumab treatment, concurring with improved and partially normalised epidermal structure, including increased FLG, CDSN, and DSG1. These data highlight Th2-skewed immunity in NS and emphasise the amelioration of NS features through dupilumab treatment. - Source: PubMed
Blunder StefanHermann-Kleiter NataschaMahmuti RitaHermann MartinOrtner DanielaReider DanielaMoosbrugger-Martinz VerenaDel Frari BarbaraStoitzner PatriziaDubrac SandrineSchmuth MatthiasGruber Robert - Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown. We profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and compared data with untreated AD and healthy control skin. We show that dupilumab treatment was accompanied by normalization of IL-4/IL-13 downstream activity markers such as CCL13, CCL17, CCL18 and CCL26. By contrast, we found strong increases in type 22-associated markers (IL22, AHR) especially in oligoclonally expanded T cells, accompanied by enhanced keratinocyte activation and IL-22 receptor upregulation. Taken together, we demonstrate that dupilumab effectively dampens conventional type 2 inflammation in DAHND lesions, with concomitant hyperactivation of IL22-associated responses. - Source: PubMed
Publication date: 2024/04/02
Bangert ChristineAlkon NataliaChennareddy SumanthArnoldner TamaraLevine Jasmine PPilz MagdalenaMedjimorec Marco ARuggiero JohnCohenour Emry RJonak ConstanzeDamsky WilliamGriss JohannesBrunner Patrick M - The Wnt family of secreted proteins are involved in mammary gland development and tumorigenesis. It has recently been shown that Wnt ligands promote M2 macrophage polarization and so we sought to determine the effects of a Wnt signaling antagonist, Secreted Frizzled Related Protein 1 (SFRP1), on M2 marker expression. We measured a murine M2 marker (Arg1) in mice with a targeted deletion of Sfrp1 during different stages of mammary gland development including puberty, pregnancy, and lactation, as well as in response to obesity. Next, to determine whether Wnt signaling/antagonism affects human M2 markers (CD209 and CCL18), we treated a human patient derived explant (PDE) breast tissue sample with exogenous Wnt3a in the presence and absence of rSFRP1. Finally, we expanded our PDE study to 13 patients and performed bulk RNAseq analysis following the treatment described above. We found that in loss of Sfrp1 in the murine mammary gland increased Arg1 expression. Moreover, we showed that Wnt3a increases CD209 and CCL18 mRNA and protein expression in breast PDEs and that their expression is decreased in response to rSFRP1. Our RNAseq analysis unveiled novel genes that were affected by Wnt3a treatment and subsequently reversed when rSFRP1 was added. Validation of these data exhibited that chemokines involved in promoting macrophage polarization and cancer metastasis, including CCL11 and CCL26, were stimulated by Wnt3a signaling and their expression was abrogated by treatment with rSFRP1. Our data suggest that SFRP1 may be an important mediator that tempers Wnt signaling in the tumor microenvironment. - Source: PubMed
Publication date: 2024/03/30
Gregory Kelly JMason HollyCasaubon JesseSchneider Sallie S - The treatment of eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) remains a challenge due to its complex pathogenesis. Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, has been implicated in allergic asthma. However, the expression and function of INPP4A in E-CRSwNP remain unclear. This study aims to investigate the role of INPP4A in macrophages in E-CRSwNP. - Source: PubMed
Publication date: 2024/02/16
Xu YingyingTong XiaotingLiu PeiqiangHuang JingyuChen SiyuanLiu DuoGu TianXie YulieGuo DuoXu Yu - This is the first report on the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the expression of skin biomarkers in patients with moderate-to-severe atopic dermatitis (AD). - Source: PubMed
Publication date: 2023/12/18
Guttman-Yassky EmmaFacheris PaolaGomez-Arias Pedro JesusDel Duca EsterDa Rosa Joel CorreaWeidinger StephanBissonnette RobertArmstrong April WSeneschal JulienEyerich KilianEstrada Yeriel DBose Swaroop NXu DanChen AllshineTatulych SvitlanaGüler ErmanChan GaryPage Karen MKerkmann Urs