Human CD40 ligand–expressing type 3 innate lymphoid cells induce IL-10–producing immature transitional regulatory B cells

Komlósi, Zsolt István; Kovács, Nóra; Veen, Willem van de; Kirsch, Anna Isabella; Fahrner, Heinz B.; Wawrzyniak, Marcin; Rebane, Ana; Stanić, Barbara; Palomares, Óscar; Rückert, Beate; Menz, Günter; Akdiş, Mübeccel; Losonczy, György

doi:10.1016/j.jaci.2017.07.046

Cited by 49 publications

(40 citation statements)

References 55 publications

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“…They are also involved in maintenance of mucosal homeostasis: human CD40L + ILC3s provide innate B cell help and are involved in an innate immunoregulatory mechanism through induction of regulatory B cell differentiation (ref. 76 and Figure 3).…”

Section: Figure 2 the Dynamic And Complex Interaction Between Risk Fmentioning

confidence: 94%

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Agache

Akdiş

2019

Journal of Clinical Investigation

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in which microRNAs (miRNAs) play a central role (Table 3). High-throughput profiling studies of well-characterized patients, including analyses of gene expression (e.g., microarrays and RNA sequencing transcriptomics), can help to identify combined signatures for type 2 and non-type 2 endotypes. They are enriching the available data for the identification of new potential targets. As critical components in the regulation of tissue homeostasis, miRNAs represent a very attractive field of precision medicine research in asthma and allergic diseases, as they have been linked to many biological mechanisms underlying Th2 cell and macrophage polarization, regulation of ILC2 biology, steroidresistant asthma phenotype, airway smooth muscle dysfunction, and impaired antiviral innate immunity (Table 3 and refs. 15-25). Thus, miRNAs represent a modifiable downstream target that will expand the precision medicine approach beyond the type 2/ non-type 2 paradigm. In one notable example of this approach, the use of gene expression microarrays on bronchial epithelial cells obtained from patients with asthma led to the identification of periostin, an IL-13-responsive biomarker (26-30). However, expression signatures are not highly specific for type 2 asthma: a recent study showed type 2 airway gene expression in a subset of patients with chronic obstructive pulmonary disease (COPD) (31).

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Section: Figure 2 the Dynamic And Complex Interaction Between Risk Fmentioning

confidence: 94%

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Agache

Akdiş

2019

Journal of Clinical Investigation

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226

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“…These IL‐15‐activated CD40L + ILC3 promoted B cell survival, proliferation, and differentiation into IL‐10, PD‐L1‐expressing functional immune transitional regulatory B cells (itB) . This suggests that ILC3s can stimulate B cell function and promote innate immune‐regulation through induction of itBreg cell differentiation . Interestingly, ILC3s are significantly increased in BAL, sputum, and peripheral blood of pediatric steroid‐resistant asthmatics compared to disease controls, and these numbers are comparable to Th17 cell numbers .…”

Section: Introductionmentioning

confidence: 93%

“…Recently, Komlosi et al. demonstrated that in response to IFN‐γ stimulation in vitro, ILC3s produce B cell‐activating factor (BAFF), that stimulates IL‐15 production by B cells, which in turn up‐regulates expression of CD40L on ILC3s in both blood and tonsillar tissue . These IL‐15‐activated CD40L + ILC3 promoted B cell survival, proliferation, and differentiation into IL‐10, PD‐L1‐expressing functional immune transitional regulatory B cells (itB) .…”

Section: Introductionmentioning

confidence: 99%

The role of type 2 innate lymphoid cells in eosinophilic asthma

Salter

Sehmi

2019

Journal of Leukocyte Biology

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Eosinophilic asthma has conventionally been proposed to be a T helper 2 driven disease but emerging evidence supports a central role of type 2 innate lymphoid cells (ILC2s). These are non-T, non-B cells that lack antigen specificity and produce more IL-5 and IL-13 than CD4 + T lymphocytes, on a cell per cell basis, in vitro. Although it is clear that ILC2s and CD4 + T cells work in concert with each other to drive type 2 immune responses, kinetic studies in allergic asthma suggest that ILC2s may act locally within the airways to "initiate" eosinophilic responses, whereas CD4 + T cells act locally and systemically to "perpetuate" eosinophilic inflammatory responses. Importantly, ILC2s are increased within the airways of severe asthmatics, with the greatest number of IL-5 + IL-13 + ILC2s being detected in sputum from severe asthmatics with uncontrolled eosinophilia despite high-dose steroid therapy. Although the precise relationship between ILC2s and steroid sensitivity in asthma remains unclear, controlling the activation of ILC2s within the airways may provide an effective therapeutic target for eosinophilic inflammation in airways diseases. K E Y W O R D Seosinophilic asthma, eosinophilopoiesis, innate lymphoid cells NMU, neuromedin U; NMUR, neuromedin U receptor; PC 20 , concentration required to achieve a 20% decrease in FEV 1 ; PLZF, pro-myelocytic leukemia zinc finger; TOX, thymocyte selection associated HMB boxprotein; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor. this review, we will discuss the role of innate lymphoid cells (ILCs) in eosinophilic asthma and the potential targets that drive persistent airway eosinophilia.

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“…ILC3 cells from peripheral blood or the tonsils expressing CD40L upon IL-15 exposure are capable of inducing IL-10 secreting immature Bregs with the help of BAFF. 49 More recently, ILCregs have been identified. These subsets were induced from ILC2 by retinoic acid and displayed typical surface markers such as CD25, CTLA-4, and produced IL-10.…”

Section: Novel Data On Clinical Markers and Biomarkers Of Food Allergymentioning

confidence: 99%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

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Human CD40 ligand–expressing type 3 innate lymphoid cells induce IL-10–producing immature transitional regulatory B cells

Cited by 49 publications

References 55 publications

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

The role of type 2 innate lymphoid cells in eosinophilic asthma

Recent developments and highlights in food allergy

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