Differential T follicular helper cell phenotypes distinguish IgE-mediated milk allergy from eosinophilic esophagitis in children.

Background: IgE-mediated food allergy and eosinophilic esophagitis (EoE) are diseases commonly triggered by milk. Milk-responsive CD4 T cells producing type 2 cytokines are present in both diseases, yet the clinical manifestation of disease in milk allergy (MA) and EoE are distinct.

Objective: We sought to identify differences in CD4 T cells between EoE and MA that may be responsible for distinct disease manifestations.

B cell memory of Immunoglobulin E (IgE) antibody responses in allergy.

Immunoglobulin E (IgE)-mediated allergic diseases are driven by high-affinity allergen-specific IgE antibodies. IgE antibodies bind to Fc epsilon receptors on mast cells, prompting their degranulation and initiating inflammatory reactions upon allergen crosslinking. While most IgE-producing plasma cells have short lifespans, and IgE memory B cells are exceedingly rare, studies have indicated that non-IgE-expressing type 2-polarized IgG memory B cells serve as a reservoir of IgE memory in allergies.

Oral tolerance to dietary antigens and Foxp3 regulatory T cells.

Immune tolerance to foods develops in the intestine upon food ingestion and is essential to prevent IgE-mediated food allergy and gut inflammation. In homeostasis, the intestine is a tolerogenic environment that favors the formation of food-specific Foxp3 regulatory T cells. A tolerogenic intestinal environment depends on colonization by diverse microbiota and exposure to solid foods at a critical period in early life.

CD23IgG1 memory B cells are poised to switch to pathogenic IgE production in food allergy.

Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23IgG1 memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23IgG1 memory B cells correlated with circulating concentrations of IgE in children with peanut allergy.

Making good of a tricky start: How IgE and mast cells manage a protective sway in food allergy.

The immune and nervous systems respond to dangerous stimuli to maintain homeostasis. In a recent issue of Nature, Florsheim et al. and Plum et al.

The memory of pathogenic IgE is contained within CD23 IgG1 memory B cells poised to switch to IgE in food allergy.

Unlabelled: Food allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23 IgG1 memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These 'type2-marked' IgG1 memory B cells differentially express IL-4/IL-13 regulated genes / , and germline and carry highly mutated B cell receptors (BCRs).

IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases.

Background: Atopic diseases are characterized by IgE antibody responses that are dependent on cognate CD4 T cell help and T cell-produced IL-4 and IL-13. Current models of IgE cell differentiation point to the role of IgG memory B cells as precursors of pathogenic IgE plasma cells. The goal of this work was to identify intrinsic features of memory B cells that are associated with IgE production in atopic diseases.

Distinct roles of ORAI1 in T cell-mediated allergic airway inflammation and immunity to influenza A virus infection.

T cell activation and function depend on Ca signals mediated by store-operated Ca entry (SOCE) through Ca release-activated Ca (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T1) cell-mediated response to influenza A virus (IAV) infection and T2 cell-mediated allergic airway inflammation. T cell-specific deletion of did not exacerbate pulmonary inflammation and viral burdens following IAV infection but protected mice from house dust mite-induced allergic airway inflammation.

Allergen recognition by specific effector Th2 cells enables IL-2-dependent activation of regulatory T-cell responses in humans.

Type 2 allergen-specific T cells are essential for the induction and maintenance of allergies to foods, and Tregs specific for these allergens are assumed to be involved in their resolution. However, it has not been convincingly demonstrated whether allergen-specific Treg responses are responsible for the generation of oral tolerance in humans. We observed that sustained food allergen exposure in the form of oral immunotherapy resulted in increased frequency of Tregs only in individuals with lasting clinical tolerance.

Immunology of COVID-19: Current State of the Science.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this Review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.

Non-classical B Cell Memory of Allergic IgE Responses.

The long-term effectiveness of antibody responses relies on the development of humoral immune memory. Humoral immunity is maintained by long-lived plasma cells that secrete antigen-specific antibodies, and memory B cells that rapidly respond to antigen re-exposure by generating new plasma cells and memory B cells. Developing effective immunological memory is essential for protection against pathogens, and is the basis of successful vaccinations.

The Secret Life of IgE-Producing Cells.

IgE antibodies are essential mediators of allergies. In a recent study in Science, Croote et al. (2018) characterize IgE cells isolated from individuals allergic to peanuts.

Variability of blood eosinophils in patients in a clinic for severe asthma.

Background: Blood eosinophils are used to determine eligibility for agents targeting IL-5 in patients with uncontrolled asthma. However, little is known about the variability of blood eosinophil measures in these patients before treatment initiation.

Objective: To characterize variability and patterns of variability of blood eosinophil levels in a real-world clinic for severe asthmatics.

Publisher Correction: IgG1 memory B cells keep the memory of IgE responses.

The originally published version of this Article contained errors in Fig. 4 that were introduced during the production process. In panel c, the two uppermost labels 'IgE spleen' and 'IgE BM' incorrectly read 'IgG1 spleen' and 'IgE1 BM', respectively.

IgG1 memory B cells keep the memory of IgE responses.

The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80CD73 and CD80CD73, contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE.

Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency.

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types.

A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues.

A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers.

The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells.

Biology of IgE production: IgE cell differentiation and the memory of IgE responses.

The generation of long-lived plasma cells and memory B cells producing high-affinity antibodies depends on the maturation of B cell responses in germinal centers. These processes are essential for long-lasting antibody-mediated protection against infections. IgE antibodies are important for defense against parasites and toxins and can also mediate anti-tumor immunity.

CD41 is a reliable identification and activation marker for murine basophils in the steady state and during helminth and malarial infections.

Basophils, a rare leukocyte population in peripheral circulation, are conventionally identified as CD45(int) CD49b(+) FcεRI(+) cells. Here, we show that basophils from blood and several organs of naïve wild-type mice express CD41, the α subunit of α(IIb)β₃ integrin. CD41 expression on basophils is upregulated after in vivo IL-3 treatment and during infection with Nippostrongylus brasiliensis (Nb).