IgE Antibody Production Research Articles

The Role of Aspergillus Antibody Detection in Allergic Bronchopulmonary Aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disorder characterized by an exaggerated immune response to fungal allergens, particularly from Aspergillus fumigatus. ABPA leads to excessive mucus production and impaired mucociliary clearance. When A. fumigatus conidia are inhaled, they germinate, release exoproteases and other substances that further impede mucociliary clearance, and activate the immune response. The immune response is known by an exaggerated Th2 response to Aspergillus antigens, leading to production of IgE antibodies, eosinophilic infiltration of the lungs, and the formation of immune complexes. These immune complexes can deposit in the lung tissue, leading to airway inflammation, bronchiectasis, and fibrosis. This disease mainly occurs in individuals diagnosed with bronchial asthma and cystic fibrosis. Increased levels of A. fumigatus total IgE and specific IgE, IgG, and IgA antibodies, play a role in diagnosing patients with ABPA.

BCR ligation selectively inhibits IgE class switch recombination.

Mechanisms that restrict class switch recombination (CSR) to IgE limit the subsequent production of IgE antibodies and therefore the development of allergic disease. Mice with impaired B cell receptor (BCR) signaling have significantly increased IgE responses, consistent with a role for BCR signaling in IgE regulation. While prior work focused on BCR signaling in IgE-expressing cells to explain these findings, it has been reported that BCR signaling can reduce CSR. Therefore, we investigated the possibility that IgE CSR might be particularly sensitive to inhibition by BCR signaling in unswitched B cells. We found that immunization of mice with high-affinity antigen resulted in reduced representation of IgE-expressing cells among germinal center B cells and plasma cells relative to a low-affinity antigen. Mechanistic experiments with cultured mouse B cells demonstrated that BCR ligands selectively inhibited IgE CSR in a dose-, affinity-, and avidity-dependent manner. Signaling via Syk was required for the inhibition of IgE CSR following BCR stimulation, whereas inhibition of the PI3K subunit p110δ increased IgE CSR independently of BCR ligation. The inhibition of IgE CSR by BCR ligands synergized with IL-21 or TGFβ1. BCR ligation also inhibited CSR to IgE in human tonsillar B cells, and this inhibition was also synergistic with IL-21. These findings establish that IgE CSR is uniquely susceptible to inhibition by BCR signaling in mouse and human B cells, with important implications for the regulation and pathogenesis of allergic disease.

Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice

BackgroundEpidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as a potential pathogenic mechanism for CMA and to elucidate the immunological mechanisms that connect lung innate immunity with CMA. MethodsMice were exposed to cow's milk (CM) treated with hydrochloric acid through repeated aspiration into their airways. Subsequently, they were challenged by intraperitoneal injection of CM extract. The immunological mechanisms were investigated using comprehensive single-cell RNA sequencing (scRNA-seq) analysis of the lungs, combined with the use of genetically modified mice. ResultsMice exposed to CM mixed with hydrochloric acid via airway sensitization developed CMA, as evidenced by the production of antigen-specific IgE and IgG antibodies, and the induction of anaphylaxis upon systemic antigen administration. In contrast, aspiration of CM alone did not induce CMA. scRNA-seq analysis revealed potential roles of alveolar macrophages in response to hydrochloric acid. Mice lacking the TLR4 pathway were protected from developing CMA. ConclusionsWe have developed a novel mouse model for CMA that utilizes the natural antigen and follows the physiological airway sensitization pathway, thus potentially resembling clinical scenarios. This model, named the acidified milk aspiration-induced allergy model, has the potential to shed light on the role of early innate immunity by analyzing a more physiological model.

Exploring the Potentiality of a Plant Platform for Monoclonal Antibody Production in Veterinary Medicine.

Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of the most effective CAD treatments is a caninized monoclonal antibody (mAb) called Lokivetmab. It is produced in CHO cells and targets specifically canine IL-31 (cIL-31) and blocks its cellular messaging. This treatment has undoubtedly contributed to a breakthrough in dermatitis-related pruritus. However, its production in mammalian cells requires time-consuming procedures, high production costs, and investment. Plants are considered an emerging protein production platform for recombinant biopharmaceuticals due to their cost-effectiveness and rapidity for production. Here, we use transient expression in Nicotiana benthamiana plants to produce recombinant canine Interleukin 31 (cIL-31) and an anti-IL-31 monoclonal antibody (M1). First, we describe the production and characterization of M1 and then its activity on an IL-31-induced pruritic model in dogs compared to its commercial homolog. Dogs treated with the plant-made M1 mAb have shown similar improvements to Lokivetmab-treated ones after different challenges using canine IL-31. Furthermore, M1 injections were not associated with any side effects. These results demonstrate the safety and efficacy of this plant-made Lokivetmab biosimilar to control dogs' pruritus in a well-established model. Finally, this study shows that the plant-production platform can be utilized to produce rapidly functional mAbs and bring hope to the immunotherapy field of veterinary medicine.

Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development.

Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future.

Exploring the immunopathology of type 2 inflammatory airway diseases.

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.

Polyethylene glycol and immunology: aspects of allergic reactions and their mechanisms, as well as ways to prevent them in clinical practice.

In modern medical practice, where polyethylene glycol is widely used as a component of various drugs, such as vaccines, chemotherapy drugs, and antibiotics, including vaccines, the issue of allergic reactions to this substance is becoming increasingly important. The purpose of this study is to review and systematise data on various aspects of allergic reactions to polyethylene glycol with the aim of better understanding their pathogenesis, clinical manifestations, diagnostic methods, and possible treatment approaches. The study analysed literature data in modern databases, such as MEDLINE, PubMed, and Scopus, on allergic reactions to polyethylene glycol, using the keywords: "PEG", "polyethylene glycol", "allergy", "side effect". The main aspects of allergy to this substance were highlighted, including mechanisms of development, diagnostic methods, and possible treatment strategies. The analysis found that allergic reactions to polyethylene glycol can manifest in a variety of ways, including anaphylaxis and systemic reactions. A possible role for the immune response has been identified, including the production of IgE and IgM antibodies, complement activation, and accelerated clearance in response to polyethylene glycol, in blood plasma. Data are also provided on how to diagnose an increased risk of an allergic reaction in patients who have previously received drugs with this type of drug transporter and in patients receiving high molecular weight types of polyethylene glycol. The results of this review contribute to a better understanding of allergic reactions to polyethylene glycol and provide information for the development of more effective diagnostic and treatment methods.

Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53.

Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.

High levels of alpha-gal with large variation in the salivary glands of lone star ticks fed on human blood

Tick bites, associated with the secretion of tick saliva containing the xenoglycan galactose-alpha-1, 3-galactose (alpha-gal or aGal), are recognized as the causal factors of alpha-Gal syndrome (AGS; or red meat allergy) in humans. AGS occurs after the increased production of IgE antibodies against aGal, which is found in most mammalian cells, except for the Old World monkey and humans. The aGal sensitization event has been linked to an initial tick bite, followed by consumption of red meat containing the aGal glycan, which triggers the onset of the allergic response resulting in urticaria, anaphylaxis, or even death. In North America, the lone star tick, Amblyomma americanum, has been identified as the main culprit for AGS. However, only a subset of the human population exposed to lone star tick bites develops AGS. This suggests the presence of unidentified variables associated with the sensitization event. To evaluate the quantitative variations of the aGal in ticks, we evaluated the differences in aGal levels in different strains of A. americanum ticks partially fed on different blood sources using an artificial feeding system and animal hosts. We found significantly higher aGal levels in the female ticks fed on human blood than those fed on the blood of other mammals with large variations among different tick populations and individuals. We propose that host-specific genetic components in the A. americanum ticks are involved in the production of high aGal epitope in the tick saliva, which provides a part of the explanation for the variables associated with the AGS sensitization event of the tick bite.

Seroprevalence of Dermatophagoides farinae-specific IgE in dogs with atopic dermatitis in São Paulo, Brazil

Canine atopic dermatitis (CAD) is a chronic, inflammatory, and pruritic disease of the skin resulting from the loss of the epidermal barrier, sensitization, and exacerbated production of IgE antibodies mainly directed against environmental allergens, especially to house dust mites. To select specific allergen immunotherapies with high efficacy, there are necessary studies with house dust mite allergens to improve both serological and intradermal tests. Therefore, the objective of this study was to evaluate the seroprevalence of IgE against Der f 2, Zen 1, and crude Dermatophagoides farinae allergens in dogs with AD in the State of São Paulo, Brazil. The sera of 85 dogs with clinically confirmed atopic dermatitis from the State of São Paulo (Brazil) was collected. In addition, an indirect ELISA test was conducted to detect allergen-specific serum IgE. IgE seropositivity was observed in 97.5% of the dogs for Der f 2, 95.0% for Zen 1, and 92.5% for the crude mite allergens. Due to this high prevalence of IgE specific to these allergens, we suggest that Der f 2 and Zen 1 can be considered major allergens for dogs in the State of São Paulo.

Dissecting Airborne Allergens.

Asthma is a heterogeneous and very complex group of diseases, and includes different clinical phenotypes depending on symptoms, progression, exacerbation patterns, or responses to treatment, among other characteristics. The allergic phenotype is the most frequent, especially in pediatric asthma. It is characterized by sensitization (the production of specific IgEs) to allergens and frequent comorbidity with rhinitis as well as atopic dermatitis. Given the complexity of allergic asthma, knowledge of it must be approached from different points of view: clinical, histological, physiological, epidemiological, biochemical, and immunological, among others. Since partial approaches do not allow for the understanding of this complexity, it is necessary to have multidimensional knowledge that helps in performing the optimal management of each case, avoiding a "blind men and elephant parable" approach. Allergens are antigens that trigger the production of specific IgE antibodies in susceptible individuals, who present symptoms that will depend on the type and intensity of the allergenic load as well as the tissue where the interaction occurs. Airborne allergens cause their effects in the respiratory tract and eyes, and can be indoor or outdoor, perennial, or seasonal. Although allergens such as mites, pollens, or animal dander are generally considered single particles, it is important to note that they contain different molecules which could trigger distinct specific IgE molecules in different patients. General practitioners, pediatricians, and other physicians typically diagnose and treat asthma based on clinical and pulmonary function data in their daily practice. This nonsystematic and nonexhaustive revision aims to update other topics, especially those focused on airborne allergens, helping the diagnostic and therapeutic processes of allergic asthma and rhinitis.

Endocannabinoid modulation of allergic responses: Focus on the control of FcεRI-mediated mast cell activation

Allergic reactions are highly prevalent pathologies initiated by the production of IgE antibodies against harmless antigens (allergens) and the activation of the high-affinity IgE receptor (FcεRI) expressed in the surface of basophils and mast cells (MCs). Research on the mechanisms of negative control of those exacerbated inflammatory reactions has been intense in recent years. Endocannabinoids (eCBs) show important regulatory effects on MC-mediated immune responses, mainly inhibiting the production of pro-inflammatory mediators. However, the description of the molecular mechanisms involved in eCB control of MC activation is far from complete. In this review, we aim to summarize the available information regarding the role of eCBs in the modulation of FcεRI-dependent activation of that cell type, emphasizing the description of the eCB system and the existence of some of its elements in MCs. Unique characteristics of the eCB system and cannabinoid receptors (CBRs) localization and signaling in MCs are mentioned. The described and putative points of cross-talk between CBRs and FcεRI signaling cascades are also presented. Finally, we discuss some important considerations in the study of the effects of eCBs in MCs and the perspectives in the field.

We are memory: B-cell responses in allergy and tolerance.

The significance of B-cell memory in sustaining IgE-mediated allergies but also ensuring the development of long-term allergen tolerance has remained enigmatic. However, well-thought murine and human studies have begun to shed more light on this highly disputed subject. The present mini review highlights important aspects, like the involvement of IgG1 memory B cells, the meaning of low- or high-affinity IgE antibody production, the impact of allergen immunotherapy, or the relevance of local memory established by ectopic lymphoid structures. Based on recent findings, future investigations should lead to deeper knowledge and the development of improved therapies treating allergic individuals.

Topical Administration of Gardenia jasminoides Extract Regulates Th2 Immunity in OVA-Induced Mice.

A key feature of an allergic immune response is a T helper type 2 (Th2)-mediated response with production of allergen-specific IgE antibodies. Gardenia jasminoides extract with the crocin removed (GJExCR) has been shown to inhibit IgE-mediated allergic disease. To evaluate the efficacy and mechanism-of-action of this inhibition, GJExCR was used in an ovalbumin (OVA)-induced allergy model in BALB/C mice. Sensitization of BALB/C mice with OVA and aluminum hydroxide was performed on days 1 and 14 by intraperitoneal injection, followed by OVA challenge to the dorsal skin for 2 weeks before removal. Seven days post-challenge, mice were treated with GJExCR topically every day for 11 days. Enzyme-linked immunosorbent assay, flow cytometry analysis, real-time PCR, and western blot were performed to determine IgE and Th2 cytokine levels. Following OVA challenge, Th2 cytokine expression and both total and OVA-specific serum IgE levels increased, of which OVA-specific IgE and Th2 cytokine levels decreased after GJExCR treatment. Flow cytometry analysis revealed that GJExCR treatment decreased CD4+ and CD8+ T cell populations in the spleen and lymph nodes. In addition, treatment with GJExCR downregulated signal transducer and activator of transcription 1 (STAT1) activation and Th2 cytokine levels as compared to control. GJExCR containing geniposide downregulated STAT1 activation in HaCaT cells. These findings demonstrate that GJExCR exerts its anti-allergy effect via inhibition of STAT1 activation, thus regulating the immune response via modulation of Th2 cytokine release and IgE levels. Therefore, we propose GJExCR as a potential treatment for allergic hypersensitivity reactions.

Preventive effect of <i>Enterococcus faecalis</i> and β-glucan on the onset and exacerbation of symptoms of atopic dermatitis in mice

<abstract> <p>Atopic dermatitis (AD) is associated with an immune response caused by the excessive production of IgE antibodies. This is accompanied by excessive itching as a clinical symptom, leading to a great burden and anxiety in daily life. At present, there is no established treatment that can completely cure AD, and symptomatic treatment alleviates symptoms to the extent that they do not interfere with daily life. Recent research has suggested that the ingestion of either various lactic acid bacteria or β-glucan suppressed the production of IgE antibodies and alleviated the symptoms of AD. Therefore, in this study, we used a drug-induced AD mouse model to evaluate the amelioration effect of EC-12 and β-glucan derived from black yeast to investigate the mechanism involved. The oral administration of lactic acid bacteria inhibited the expression of inflammatory cytokine genes at the lesion site, and the administration of β-glucan downregulated serum IgE levels and inhibited the expression of inflammatory cytokine genes at the lesion site. The concomitant administration of EC-12 and β-glucan strongly suppressed AD symptoms, downregulated serum IgE levels, and inhibited the expression of inflammatory cytokines at the lesion site. In summary, the oral administration of EC-12 and β-glucan prevented AD in mice.</p> </abstract>

Effects of Immunization with Recombinant Schistosoma mansoni Enzymes AK and HGPRT: Murine Infection Control.

Schistosomiasis is one of the most important human helminthiases worldwide. Praziquantel is the current treatment, and no vaccine is available until the present. Thus, the presented study aimed to evaluate the immunization effects with recombinant Schistosoma mansoni enzymes: Adenosine Kinase (AK) and Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT), as well as a MIX of the two enzymes. Female Balb/c mice were immunized in three doses, and 15 days after the last immunization, animals were infected with S. mansoni. Our results showed that the group MIX presented a reduction in the eggs in feces by 30.74% and 29%, respectively, in the adult worms. The groups AK, HGPRT and MIX could produce IgG1 antibodies, and the groups AK and MIX produced IgE antibodies anti-enzymes and anti-S. mansoni total proteins. The groups AK, HGPRT and MIX induced a reduction in the eosinophils in the peritoneal cavity. Besides, the group AK showed a decrease in the number of hepatic granulomas (41.81%) and the eggs present in the liver (42.30%). Therefore, it suggests that immunization with these enzymes can contribute to schistosomiasis control, as well as help to modulate experimental infection inducing a reduction of physiopathology in the disease.

Feasibility of plant-expression system for production of recombinant anti-human IgE: An alternative production platform for therapeutic monoclonal antibodies.

Omalizumab, the anti-immunoglobulin IgE antibody is the only approved and available monoclonal antibody as an auxiliary medicament for the severe respiratory allergic reactions. It forms small size immune complexes by binding to free IgE, thereby inhibiting the interaction of IgE with its receptors. Additionally, the anti-IgE can also differently shape the airflow by impeding the stimulation of IgE receptors present on structural cells in the respiratory tract. The present study aimed to use plants as an expression system for anti-human IgE antibody production, using Nicotiana benthamiana as hosts. Recombinant Agrobacterium tumefaciens containing heavy chain (HC) and light chain (LC) domains of anti-human IgE were co-transformed in N. benthamiana. The assembling of the antibody and its expression was detected by SDS-PAGE and Western blot analysis. The functional ability of the anti-IgE antibody was determined via its binding capacity with target IgE by ELISA and the inhibition of basophil activation. The anti-human IgE mAb generated in plants was shown to be effective in binding to its target IgE and inhibit the IgE-crosslink in RS-ATL8 reporter cells. Although, antibody yield and purification process have to be further optimized, this study demonstrates the use of plant expression system as a promising platform for the production of Omalizumab which showed a comparable in vitro function to that of commercial Omalizumab (Xolair) in the inhibition of basophil activation.

BCL6 deletion in CD4 T cells does not affect Th2 effector mediated immunity in the skin.

Recent studies propose that T follicular helper (Tfh) cells possess a high degree of functional plasticity in addition to their well-defined roles in mediating interleukin-4-dependent switching of germinal center B cells to the production of immunoglobulin (Ig)G1 and IgE antibodies. In particular Tfh cells have been proposed to be an essential stage in Th2 effector cell development that are able to contribute to innate type 2 responses. We used CD4-cre targeted deletion of BCL6 to identify the contribution Tfh cells make to tissue Th2 effector responses in models of atopic skin disease and lung immunity to parasites. Ablation of Tfh cells did not impair the development or recruitment of Th2 effector subsets to the skin and did not alter the transcriptional expression profile or functional activities of the resulting tissue resident Th2 effector cells. However, the accumulation of Th2 effector cells in lung Th2 responses was partially affected by BCL6 deficiency. These data indicate that the development of Th2 effector cells does not require a BCL6 dependent step, implying Tfh and Th2 effector populations follow separate developmental trajectories and Tfh cells do not contribute to type 2 responses in the skin.

Yer Fıstığında Bulunan Alerjenler ve Alerjen Etkiyi Azaltma Yöntemleri

Peanut allergens adversely affect the health and quality of life of millions of consumers worldwide. The seeds of the peanut plant (Arachis hypogaea L.) contain a number of allergens that trigger the production of specific IgE antibodies in allergy-prone individuals. Currently, 18 proteins found in peanuts are accepted as allergens. These allergens are named from Ara h 1 to Ara h 18. Ara h 2, Ara h 6 and Ara h 7 are from albumin, Ara h 1 and Ara h 3 are from globülin. Ara h is the abbreviation of Arachis hypogaea, the Latin name for peanut. A peanut allergy is a reaction that occurs shortly after eating to peanuts or peanut products. It has various symptoms that can go up to swelling of the tongue, itching of the palate, itching and burning in the throat, itching in the eyes and nose, nausea, vomiting, abdominal pain, shortness of breath, wheezing, bruising, chest pain, hives, low blood pressure and shock. In this review, the properties of peanut allergens and the methods of reducing the allergen effect will be reviewed.

Heterogeneity, subsets, and plasticity of T follicular helper cells in allergy

Antibody responses are critical for protection against pathogens. However, diseases such as allergic rhinitis or food allergy result from aberrant production of IgE antibodies against otherwise innocuous environmental antigens. The production of allergen-specific IgE requires interaction between B cells and CD4⁺ T cells, and a granular understanding of these interactions is required to develop novel therapies for allergic disease. CD4⁺ T cells are exceptionally heterogeneous in their transcriptional, epigenetic, and proteomic profiles, which poses significant challenges when attempting to define subsets relevant to the study of allergy among a continuum of cells. Defining subsets such as the T follicular helper (T_FH) cell cluster provides a shorthand to understand the functions of CD4⁺ T cells in antibody production and supports mechanistic experimentation for hypothesis-driven discovery. With a focus on allergic disease, this Rostrum article broadly discusses heterogeneity among CD4⁺ T cells and provides a rationale for subdividing T_FH cells into both functional and cytokine-skewed subsets. Further, it highlights the plasticity demonstrated by T_FH cells during the primary response and after recall, and it explores the possibility of harnessing this plasticity to reprogram immunity for therapeutic benefit in allergic disease.