Chronic spontaneous urticaria (CSU) is defined as recurrent episodes of spontaneous wheal development and/or angioedema for more than six weeks and at least twice a week. The core link in the pathogenesis of CSU is the activation of mast cells, T cells, eosinophils, and other immune cells infiltrating around the small venules of the lesion. Increased vascular permeability, vasodilatation, and recruitment of inflammatory cells directly depend on mast cell mediators’ release. Complex regulatory systems tightly influence the critical roles of mast cells in the local microenvironment. The bias toward Th2 inflammation and autoantibodies derived from B cells, histamine expressed by basophils, and initiation of the extrinsic coagulation pathway by eosinophils or monocytes exerts powerful modulatory influences on mast cells. Cell-to-cell interactions between mast cells and eosinophils/T cells also are regulators of their function and may involve CSU’s pathomechanism. This review summarizes up-to-date knowledge regarding the crosstalk between mast cells and other immune cells, providing the impetus to develop new research concepts and treatment strategies for CSU.

Chronic urticaria (CU) is a chronic inflammatory skin disease mainly mediated by mast cells. Lipids exert essential functions in biological processes; however, the role of lipids in CU remains unclear. Nontargeted lipidomics was performed to investigate the differential lipid profiles between CU patients and healthy control (HC) subjects. Functional validation studies were performed in vitro and in vivo including β-hexosaminidase release examination from mast cells and passive cutaneous anaphylaxis (PCA) mouse model. We detected dramatically altered glycerophospholipids in CU patients compared with HCs. Phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) were increased, while phosphatidylcholine (PC) was reduced in CU patients. The reduction in PC was related to a high weekly urticaria activity score (UAS7), while PS was positively associated with the dermatology life quality index (DLQI). We also identified the differential lipid profiles between chronic spontaneous urticaria (CSU), symptomatic dermographism (SD), and CSU coexist with SD. CU patients were classified into two subtypes (subtype 1 and subtype 2) based on consensus clustering of lipid profiling. Compared with patients in subtype 2, patients in subtype 1 had elevated levels of PC (18:0e/18:2) and PE (38:2), and lower urticaria control test (UCT) scores indicated worse clinical efficiency of secondary generation H1 antihistamines treatment. Importantly, we found that supplementation with PC could attenuate IgE-induced immune responses in mast cells. In general, We described the landscape of plasma lipid alterations in CU patients and provided novel insights into the role of PC in mast cells.

BackgroundAtopic dermatitis (AD) is a common skin disease, but treatment of this disease has been challenging. Dupilumab is a new biological agent for AD that has been proven to be safe and effective in clinical trials. Although dupilumab was approved for listing in China in June 2020, real-world data about the application of dupilumab in China are lacking. This study aimed to collect and analyze real-world data on dupilumab among Chinese AD patients.MethodsDemographic and clinical data for 116 AD patients receiving dupilumab treatment were reviewed. The Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) of patients were evaluated every 2 weeks from baseline to 16 weeks of treatment. Any adverse events during treatment were recorded.ResultsAmong the 116 patients in this study, baseline levels of IgE, eosinophils, and LDH were elevated in 62.79% (n = 86), 45.30% (n = 86), and 54.20% of patients (n = 48), respectively. The SCORAD index and POEM, DLQI, and NRS scores were significantly improved in all patients at 2 weeks (p < 0.0001), 4 weeks (p < 0.01), and 16 weeks (p < 0.001). EASI scores also improved significantly in all patients at 2 weeks (p < 0.01), 4 weeks (> 0.05), and 16 weeks (p < 0.01). However, 11 patients (9.48%) had no response. IgE and LDH levels (p > 0.05), Eosinophil counts (p < 0.01) in blood increased temporarily in the first 4 weeks and then decreased and stabilized during dupilumab treatment. Conjunctivitis was the most common adverse event (2.59%) among the patients. We found that the curative efficacy of dupilumab at 4th weeks was related to the patient’s age and course of disease. Nevertheless, there is no relationship between levels of eosinophils, IgE, LDH and the therapeutic efficacy of dupilumab.ConclusionThe real-world data in China showed that dupilumab can effectively treat AD and is well tolerated with a low incidence of adverse events.

Three distinctly different alleles of the metallothionein gene Mtn have been identified in natural Drosophila melanogaster populations: Mtn.3, Mtn1, and Dp(Mtn1), where the latter designates a tandem duplication of Mtn1. In Drosophila simulans, only Mtn.3-type alleles have been found. It has been suggested that Mtn.3 is the ancestral allele and demonstrated that a presumed two-step transition from Mtn.3 to Mtn1 to Dp(Mtn1) is accompanied by an approximate 5-fold increase in RNA levels. We analyzed the evolutionary genetics of the Mtn locus of Drosophila ananassae, a distant relative of D. melanogaster and D. simulans within the melanogaster species group. The Mtn gene of D. ananassae is most similar to Mtn.3: (i) it is identical with Mtn.3 at the amino acid level, but differs from Mtn1 in its terminal codon; (ii) its 3' UTR contains a characteristic extra DNA segment of about 50 bp which is present in Mtn.3, but lacking in Mtn1; (iii) duplications of Mtn were not found in a worldwide sample of 110 wild D. ananassae chromosomes. However, the intron of the Mtn gene in D. ananassae is only 69 bp long, whereas the length of the Mtn.3 and Mtn1 introns is 265 bp; and it lacks a polypyrimidine stretch upstream of the 3' splice site in contrast to the much greater pyrimidine-richness found in the Mtn.3 and Mtn1 introns. A short intron (67 bp) was also identified in a D. pseudoobscura Mtn allele, suggesting that the short intron is the ancestral form and that the transition from the short to the long intron occurred within the melanogaster species group.(ABSTRACT TRUNCATED AT 250 WORDS)

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