IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG

memory B cells, as IgE

memory B cells and IgE

plasma cells are extremely scarce and short-lived, respectively.

Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy.

We used a novel human PBMC culture platform, a mouse model of peanut allergy, and various experimental readouts to assess the IgE recall response in the presence and absence of IL-4Rα blockade.

In human PBMCs, we have demonstrated that blockade of IL-4/IL-13 signaling aborted IgE production after activation of a recall response and skewed the cytokine response away from a dominant type 2 signature. T

2A cells, identified by single-cell RNA sequencing, expanded with peanut stimulation and maintained their pathogenic phenotype in spite of IL-4Rα blockade. In mice with allergy, anti-IL-4Rα provided long-lasting suppression of the IgE recall response beyond antibody treatment and fully protected against anaphylaxis.

The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.

The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.

Mixed connective tissue disease (MCTD) is a rare and complex autoimmune disease that presents mixed features with other connective tissue diseases, such as systemic lupus erythematosus, systemic sclerosis, and myositis. It is characterized by high levels of anti-U1 small nuclear ribonucleoprotein 70k autoantibodies and a high incidence of life-threatening pulmonary involvement. The pathophysiology of MCTD is not well understood, and no specific treatment is yet available for the patients. Basophils and IgE play a role in the development of systemic lupus erythematosus and thus represent new therapeutic targets for systemic lupus erythematosus and other diseases involving basophils and IgE in their pathogenesis.

We sought to investigate the role of basophils and IgE in the pathophysiology of MCTD.

Basophil activation status and the presence of autoreactive IgE were assessed in peripheral blood of a cohort of patients with MCTD and in an MCTD-like mouse model. LY2880070 solubility dmso Basophil depletion and IgE-deficient animals were used to investigate the contribution of basophils and IgE in the lung pathology development of this mouse model.

Patients with MCTD have a peripheral basopenia and activated blood basophils overexpressing C-C chemokine receptor 3. Autoreactive IgE raised against the main MCTD autoantigen U1 small nuclear ribonucleoprotein 70k were found in nearly 80% of the patients from the cohort. Basophil activation and IgE anti-U1 small nuclear ribonucleoprotein 70k were also observed in the MCTD-like mouse model along with basophil accumulation in lymph nodes and lungs. Basophil depletion dampened lung pathology, and IgE deficiency prevented its development.

Basophils and IgE contribute to MCTD pathophysiology and represent new candidate therapeutic targets for patients with MCTD.

Basophils and IgE contribute to MCTD pathophysiology and represent new candidate therapeutic targets for patients with MCTD.

Janus kinase (JAK) inhibitors are a new class of therapeutic compounds for dermatological diseases. In atopic dermatitis (AD), data of clinical phase III trials show rapid improvement of pruritus and significant reduction of inflammation within the first weeks with a favorable safety profile. However, their mode of action in AD is not fully understood.

In our study, we investigate the effect of different JAK inhibitors on cell differentiation, phenotype, and function of inflammatory dendritic epidermal cells (IDECs).

We analyzed the JAK expression in IDEC from exvivo skin and invitro generated IDECs using flow cytometry and PCR. Further, we studied invitro the effect of different JAK inhibitors on IDEC cell differentiation, phenotype, and maturation.

IDECs express JAK1 and JAK2 exvivo and invitro. We found that JAK1 and JAK2 were upregulated during the differentiation from monocytes to IDECs. Conversely, JAK2 inhibition by ruxolitinib (JAK1/2 inhibitor) or BMS-911543 (JAK2 inhibitor) abrogated the differentiation from monocytes into IDECs. Differentiated IDECs can redifferentiate into a more monocyte-like phenotype in the presence of ruxolitinib or BMS-911543. Furthermore, we showed that concomitant inhibition of JAK1/2 rather than blocking JAK1 or JAK2 alone, impaired maturation and the release of proinflammatory cytokines on lipopolysaccharide stimulation.

Our results suggest that inhibition of JAK1/2 impairs IDEC differentiation and function. We provide new insight into the mode of action of JAK inhibitors in AD and highlight the role of JAK1/2 inhibitors for the treatment of patients with AD.

Our results suggest that inhibition of JAK1/2 impairs IDEC differentiation and function. We provide new insight into the mode of action of JAK inhibitors in AD and highlight the role of JAK1/2 inhibitors for the treatment of patients with AD.

Urbanization is linked with an increased burden of asthma and atopic traits. Aputative mechanism is insufficient exposure to beneficial microbes early in life, leading to immune dysregulation, as was previously shown for indoor microbial exposures.

Our aim was to investigate whether urbanization is associated with the microbiota composition in the infants’ body and early immune function, and whether these contribute to the later risk of asthma and atopic traits.

We studied the prospective Copenhagen Prospective Studies on Asthma in Childhood 2010

mother-child cohort of 700 children growing up in areas with different degrees of urbanization. During their first year of life, airway and gut microbiotas, as well as immune marker concentrations, were defined. When the children were 6 years of age, asthma and atopic traits were diagnosed by pediatricians.

In adjusted analyses, the risk of asthma and aeroallergen sensitization were increased in urban infants. The composition of especially airway but also gut microbiotas differed between urban and rural infants.