Complex 2B4 Regulation of Mast Cells and Eosinophils in Murine Allergic Inflammation

The cell surface molecule 2B4 (CD244) is an important regulator of lymphocyte activation, and its role in antiviral immunity and lymphoproliferative disorders is well established. Although it is also expressed on mast cells (MCs) and eosinophils (Eos), the functions of 2B4 on these allergy-orchestrating cells remain unclear. We therefore investigated the role of 2B4 on murine MCs and Eos, particularly how this molecule affects allergic and nonallergic inflammatory processes involving these effector cells. Experiments in bone marrow–derived cultures revealed an inhibitory effect for 2B4 in MC degranulation, but also an opposing stimulatory effect in eosinophil migration and delayed activation. Murine disease models supported the dual 2B4 function: In 2B4-/- mice with nonallergic peritonitis and mild atopic dermatitis (AD), modest infiltrates of Eos into the peritoneum and skin (respectively) confirmed that 2B4 boosts eosinophil trafficking. In a chronic AD model, 2B4-/- mice showed overdegranulated MCs, confirming the inhibiting 2B4 effect on MC activation. This multifunctional 2B4 profile unfolded in inflammation resembles a similar mixed effect of 2B4 in natural killer cells. Taken together, our findings provide evidence for physiological 2B4 stimulatory/inhibitory effects in MCs and Eos, pointing to a complex role for 2B4 in allergy

Microbe-host interplay in atopic dermatitis and psoriasis

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.Peer reviewe

Evaluation of Soluble CD48 Levels in Patients with Allergic and Nonallergic Asthma in Relation to Markers of Type 2 and Non-Type 2 Immunity: An Observational Study

CD48 is a costimulatory receptor associated with human asthma. We aimed to assess the significance of the soluble form of CD48 (sCD48) in allergic and nonallergic asthma. Volunteer patients completed an asthma and allergy questionnaire, spirometry, methacholine challenge test, a common allergen skin prick test, and a complete blood count. sCD48, IgE, IL5, IL17A, IL33, and IFNγ were quantitated in serum by ELISA. Asthma was defined as positive methacholine challenge test or a 15% increase in FEV1 post bronchodilator in symptomatic individuals. Allergy was defined as positive skin test or IgE levels > 200 IU/l in symptomatic individuals. 137 individuals participated in the study: 82 (60%) were diagnosed with asthma of which 53 (64%) was allergic asthma. sCD48 levels were significantly elevated in patients with nonallergic asthma compared to control and to the allergic asthma cohort (median (IQR) pg/ml, 1487 (1338–1758) vs. 1308 (1070–1581), p<0.01, and 1336 (1129–1591), p=0.02, respectively). IL17A, IL33, and IFNγ levels were significantly elevated in allergic and nonallergic asthmatics when compared to control. No correlation was found between sCD48 level and other disease markers. sCD48 is elevated in nonallergic asthma. Additional studies are required for understanding the role of sCD48 in airway disease