Dominant immune tolerance in the intestinal tract imposed by RelB-dependent migratory dendritic cells regulates protective type 2 immunity.

Dendritic cells (DCs) are crucial for initiating protective immune responses and have also been implicated in the generation and regulation of Foxp3 regulatory T cells (Treg cells). Here, we show that in the lamina propria of the small intestine, the alternative NF-κB family member RelB is necessary for the differentiation of cryptopatch and isolated lymphoid follicle-associated DCs (CIA-DCs). Moreover, single-cell RNA sequencing reveals a RelB-dependent signature in migratory DCs in mesenteric lymph nodes favoring DC-Treg cell interaction including elevated expression and release of the chemokine CCL22 from RelB-deficient conventional DCs (cDCs).

Basophil activation in insect venom allergy: comparison of an established test using liquid reagents with a test using 5-color tubes with dried antibody reagents.

Background: Flow cytometry-based basophil activation tests (BAT) have been performed with various modifications, differing in the use of distinct identification and activation markers. Established tests use liquid reagents while a new development involves the use of tubes with dried antibody reagents. The aim of this pilot study was to compare these two techniques in patients with insect venom allergy.

The atypical IκB family member Bcl3 determines differentiation and fate of intestinal RORγt regulatory T-cell subsets.

Peripherally-induced regulatory T cells (pTregs) expressing the retinoic acid receptor-related orphan-receptor gamma t (RORγt) are indispensable for intestinal immune homeostasis. Nuclear factor kappa family members regulate the differentiation of thymic Tregs and promote their survival in the periphery. However, the Treg intrinsic molecular mechanisms controlling the size of the pTregs in the intestine and associated lymphoid organs remain unclear.

Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis.

The prevalence of food allergy is rising and is estimated to approach 10%. Red meat allergy is the first known food allergy elicited by immunoglobulin E (IgE) antibodies recognizing a carbohydrate. Due to the loss of function of the alpha-1,3-galactosyltransferase ( gene in humans, the disaccharide galactose-α-1,3-galactose (α-Gal) cannot be synthesized and therefore became immunogenic.

Kidins220 regulates the development of B cells bearing the λ light chain.

The ratio between κ and λ light chain (LC)-expressing B cells varies considerably between species. We recently identified Kinase D-interacting substrate of 220 kDa (Kidins220) as an interaction partner of the BCR. ablation of Kidins220 in B cells resulted in a marked reduction of λLC-expressing B cells.

IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.

Background: Alpha-gal (Galα1-3Galβ1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood.

Inflammatory Cues Direct Skin-Resident Type 1 Innate Lymphoid Cells to Adopt a Psoriasis-Promoting Identity.

Innate lymphoid cells (ILCs) are gatekeepers in barrier organs, where they maintain tissue integrity and contribute to host defense as well as tissue repair. Inappropriate activation of ILCs, however, can lead to immunopathology with detrimental results. In this study, we focused on type 1 ILCs (ILC1s), which under inflammatory conditions constitute a poorly defined population with ambiguous functions.

Munich atopy prediction study (MAPS): protocol for a prospective birth cohort addressing clinical and molecular risk factors for atopic dermatitis in early childhood.

Introduction: The pathogenesis of atopic diseases is highly complex, and the exact mechanisms leading to atopic dermatitis (AD) onset in infants remain mostly enigmatic. In addition to an interdependent network of components of skin development in young age and skin barrier dysfunction underlying AD development that is only partially understood, a complex interplay between environmental factors and lifestyle habits with skin barrier and immune dysregulation is suspected to contribute to AD onset. This study aims to comprehensively evaluate individual microbiome and immune responses in the context of environmental determinants related the risk of developing AD in the first 4 years of a child's life.

Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation.

The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrome P450 (CYP1) family members contribute to the regulation of allergic airway inflammation remains unexplored. By employing knockout mice for AhR and for single CYP1 family members, we found that AhR and CYP1B1 but not CYP1A1 or CYP1A2 animals display enhanced allergic airway inflammation compared to WT.

Fetal Tissue-Derived Mast Cells (MC) as Experimental Surrogate for In Vivo Connective Tissue MC.

Bone-marrow-derived mast cells are matured from bone marrow cells in medium containing 20% fetal calf serum (FCS), interleukin (IL)-3 and stem-cell factor (SCF) and are used as in vitro models to study mast cells (MC) and their role in health and disease. In vivo, however, BM-derived hematopoietic stem cells account for only a fraction of MC; the majority of MC in vivo are and remain tissue resident. In this study we established a side-by-side culture with BMMC, fetal skin MC (FSMC) or fetal liver MC (FLMC) for comparative studies to identify the best surrogates for mature connective tissue MC (CTMC).

The History of Carbohydrates in Type I Allergy.

Although first described decades ago, the relevance of carbohydrate specific antibodies as mediators of type I allergy had not been recognized until recently. Previously, allergen specific IgE antibodies binding to carbohydrate epitopes were considered to demonstrate a clinically irrelevant cross-reactivity. However, this changed following the discovery of type I allergies specifically mediated by oligosaccharide structures.

Proximal Promoter-Driven Function Is Limited in Neonatal and Ineffective in Adult γδ T Cell Development.

During T cell development, gene expression is temporally controlled by its proximal and distal promoters. The transgenic mouse available from The Jackson Laboratory, in which the proximal promoter of drives expression, is a commonly used driver line to recombine genes flanked by sites in T cells. drives recombination early in thymocyte development and is frequently used to delete genes in αβ and γδ T cells.

The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification.

The apparition of adaptive immunity in correlates with the expansion of the E-protein family to encompass E2-2, HEB, and E2A. Within the family, E2-2 and HEB are more closely evolutionarily related but their concerted action in hematopoiesis remains to be explored. Here we show that the combined disruption of E2-2 and HEB results in failure to express the early lymphoid program in Common lymphoid precursors (CLPs) and a near complete block in B-cell development.

Regulatory T cells characterized by low Id3 expression are highly suppressive and accumulate during chronic infection.

Foxp3 regulatory T (Treg) cells are broadly divided into naive-like and activated Treg cells, however recent studies suggest further Treg cell heterogeneity. Treg cells contribute to impaired T cell responses in chronic infections, but the role of specific Treg cell subpopulations in viral infections is not well defined. Here, we report that activated Treg cells are separated into two transcriptionally distinct subpopulations characterized by low or high expression of the transcriptional regulator .

The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development.

During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14.

Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3.

The transcription factor Foxp3 dominantly controls regulatory T (Treg) cell function, and only its continuous expression guarantees the maintenance of full Treg cell-suppressive capacity. However, transcriptional regulators maintaining Foxp3 transcription are incompletely described. Here, we report that high E47 transcription factor activity in Treg cells resulted in unstable Foxp3 expression.

The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes.

Adult neural stem/precursor cells (NSPCs) of the subventricular zone (SVZ) are an endogenous source for neuronal replacement in CNS disease. However, adult neurogenesis is compromised after brain injury in favor of a glial cell fate, which is mainly attributed to changes in the NSPC environment. Yet, it is unknown how this unfavorable extracellular environment translates into a transcriptional program altering NSPC differentiation.