Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis.

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

[Clinical characteristics of urticaria in children versus adults].

OBJECTIVE: To study the clinical characteristics of urticaria in children versus adults, and to provide reference for the etiological analysis, disease evaluation, and treatment of urticaria in children. METHODS: The clinical data of 2 411 patients with urticaria who visited the Department of Dermatology at Xiangya Hospital of Central South University from January 2013 to May 2017 were collected to study their socio-demographic characteristics. The clinical characteristics of urticaria were compared between the 68 children and 672 adults of the 740 patients with complete follow-up data. RESULTS: Among the 411 pediatric patients, 314 (76.4%) had acute urticaria; among the 2 000 adult patients, 896 (44.8%) had chronic spontaneous urticaria. The causes of acute urticaria in children included infection (41%, 16/39). The accompanying symptoms of acute urticaria in children mainly included abdominal pain and diarrhea (44%, 17/39), while those in adults mainly included chest distress and shortness of breath (32%, 11/34). Compared with the adult patients, the pediatric patients had significantly lower chronic urticaria activity scores before and after treatment (P<0.05), a significantly higher rate of response to second-generation antihistamines (82.1% vs 62.2%; P<0.05), and a significantly higher proportion of individuals with a personal and family history of urticaria (P<0.05). CONCLUSIONS: Acute urticaria is more commonly seen than chronic urticaria in children with urticaria, and the main accompanying symptoms are abdominal pain and diarrhea, which are different from adults with urticaria. Chronic urticaria has a better treatment outcome in children than in adults. The most frequently seen cause of acute urticaria is infection in children. Atopic children may be susceptible to urticaria.