ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Hierarchical IL-5 expression defines a subpopulation of highly differentiated human Th2 cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 114 citations in OpenAlex.
- Allergen-specific T cells and clinical features of food allergy: Lessons from CoFAR immunotherapy cohorts.The Journal of allergy and clinical immunology · 2022Trial
- Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection and Risk in RTS,S/AS01E Vaccinees.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017Trial
- A phenotypically and functionally distinct human TScience translational medicine · 2017Trial
- A pilot study of omalizumab in eosinophilic esophagitis.PloS one · 2015Trial
- Pathogenic type-2 immunity beyond allergy: the role of Th2 cell heterogeneity in helminth infections.Infection and immunity · 2026Review
- Review
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- Tertiary lymphoid structures support the development of allergen-specific progenitor CD4+ T cells.bioRxiv : the preprint server for biology · 2025Article
- Biomarker-driven drug development for allergic diseases and asthma: An FDA public workshop.The Journal of allergy and clinical immunology · 2025Article
- Differential T follicular helper cell phenotypes distinguish IgE-mediated milk allergy from eosinophilic esophagitis in children.The Journal of allergy and clinical immunology · 2025Article
- Tissue-Resident Th2 Cells in Type 2 Immunity and Allergic Diseases.Immunological reviews · 2025Review
- Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona.Frontiers in public health · 2025Article
- Contribution of T cell subsets to different food allergic diseases.Immunological reviews · 2024Review
- TL1A priming induces a multi-cytokine Th9 cell phenotype that promotes robust allergic inflammation in murine models of asthma.Mucosal immunology · 2024Article
- Triggers for eosinophilic esophagitis (EoE): The intersection of food allergy and EoE.The Journal of allergy and clinical immunology · 2024Review
- TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TNature immunology · 2024Article
- Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis.The European respiratory journal · 2024Article
- Identification of a human multipotent TNature immunology · 2024Article
- TSLP shapes the pathogenic responses of memory CD4Science signaling · 2023Article
- The ins and outs of innate and adaptive type 2 immunity.Immunity · 2023Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Each of the three Th2 cytokine genes, IL-4, IL-5, and IL-13, has different functions. We hypothesized that Th2 heterogeneity could yield Th2 subpopulations with different cytokine expression and effector functions. Using multiple approaches, we demonstrate that human Th2 cells are composed of two major subpopulations: a minority IL-5(+) (IL-5(+), IL-4(+), IL-13(+)) and majority IL-5(-) Th2 (IL-5(-), IL-4(+), IL-13(+)) population. IL-5(+) Th2 cells comprised only 20% of all Th2 cells. Serial rounds of in vitro differentiation initially yielded IL-5(-) Th2, but required multiple rounds of differentiation to generate IL-5(+) Th2 cells. IL-5(+) Th2 cells expressed less CD27 and greater programmed cell death-1 than IL-5(-) Th2 cells, consistent with their being more highly differentiated, Ag-exposed memory cells. IL-5(+) Th2 cells expressed greater IL-4, IL-13, and GATA-3 relative to IL-5(-) Th2 cells. GATA-3 and H3K4me(3) binding to the IL5 promoter (IL5p) was greater in IL-5(+) relative to IL-5(-) Th2 cells, whereas there was no difference in their binding to the IL4p and IL13p. Conversely, H3K27me(3) binding to the IL5p was greater in IL-5(-) Th2 cells. These findings demonstrate Th2 lineage heterogeneity, in which the IL5 gene is regulated in a hierarchical manner relative to other Th2 genes. IL-5(+) Th2 cells are phenotypically distinct and have epigenetic changes consistent with greater IL5p accessibility. Recurrent antigenic exposure preferentially drives the differentiation of IL-5(+) Th2 cells. These results demonstrate that IL-5(+) and IL-5(-) Th2 cells, respectively, represent more and less highly differentiated Th2 cell subpopulations. Such Th2 subpopulations may differentially contribute to Th2-driven pathology.
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