{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The high‐affinity IgE receptor α chain, encoded by the FCER1A gene, plays a pivotal role in IgE‐mediated immune responses. Its protein product is essential for binding IgE on various effector cells, including mast cells, basophils, and plasmacytoid dendritic cells, thus initiating cellular activation that leads to mediator release such as histamine and cytokines. Structural studies have elucidated that upon binding IgE, the receptor undergoes conformational changes that not only stabilize the interaction but also underlie its uniquely slow IgE dissociation kinetics, which are critical for sustained signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, functional genomic studies have consistently linked polymorphisms in FCER1A with differences in total serum IgE levels and allergic sensitization. For example, genome‐wide association studies have shown that common variants in the FCER1A locus are strongly associated with elevated IgE concentrations and may predispose individuals to allergic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n On a cellular level, cross‐linking of FcεRI on plasmacytoid dendritic cells and basophils modulates cell activation and cytokine production. In these cells, engagement of the receptor can lead to decreased antiviral interferon responses or enhanced release of pro‐inflammatory mediators, thereby influencing the balance between innate and adaptive immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, aberrant levels of receptor expression—as observed in patients with conditions such as chronic idiopathic urticaria or aspirin‐induced hypersensitivity—are linked to exaggerated histamine release and altered functional responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Transcriptional regulation of FCER1A is tightly controlled; transcription factors such as GATA2 are indispensable for maintaining FCER1A mRNA and protein expression in both mast cells and basophils, ensuring proper receptor assembly and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Additionally, therapeutic interventions that alter circulating IgE levels, such as treatment with omalizumab, can modify the stoichiometry of the receptor subunits on basophils—resulting in increased expression of intracellular signaling components (for example, Syk) and altered cell responsiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, emerging evidence even suggests that variation in FCER1A can have implications beyond classical allergic disorders, with certain polymorphisms being associated with susceptibility to other immune‐mediated conditions such as breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the central role of FCER1A in orchestrating IgE‐dependent cellular responses and highlight its importance as both a regulatory molecule of allergic inflammation and a potential target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mary D Holdom, Anna M Davies, Joanne E Nettleship, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor FcɛRI."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2044"}], "href": "https://doi.org/10.1038/nsmb.2044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21516097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21516097"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Stephan Weidinger, Christian Gieger, Elke Rodriguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000166"}], "href": "https://doi.org/10.1371/journal.pgen.1000166"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18846228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18846228"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Michelle A Gill, Gagan Bajwa, Tiffany A George, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0901194"}], "href": "https://doi.org/10.4049/jimmunol.0901194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20410486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20410486"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "John T Schroeder, Anja P Bieneman, Huiqing Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR9- and FcepsilonRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.175.9.5724"}], "href": "https://doi.org/10.4049/jimmunol.175.9.5724"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16237063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16237063"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "John A Eckman, Robert G Hamilton, Laura M Gober, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Basophil phenotypes in chronic idiopathic urticaria in relation to disease activity and autoantibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2008.55"}], "href": "https://doi.org/10.1038/jid.2008.55"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18356810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18356810"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jin-Sik Bae, Seung-Hyun Kim, Young-Min Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Significant association of FcepsilonRIalpha promoter polymorphisms with aspirin-intolerant chronic urticaria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2006.10.006"}], "href": "https://doi.org/10.1016/j.jaci.2006.10.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17125826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17125826"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yapeng Li, Xiaopeng Qi, Bing Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The STAT5-GATA2 pathway is critical in basophil and mast cell differentiation and maintenance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1500018"}], "href": "https://doi.org/10.4049/jimmunol.1500018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25801432"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25801432"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Asifa K Zaidi, Sarbjit S Saini, Donald W Macglashan "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Syk kinase and FcRbeta expression in human basophils during treatment with omalizumab."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2009.12.996"}], "href": "https://doi.org/10.1016/j.jaci.2009.12.996"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20236696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20236696"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ji-Young Lee, Ae Kyung Park, Kyoung-Mu Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Candidate gene approach evaluates association between innate immunity genes and breast cancer risk in Korean women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgp084"}], "href": "https://doi.org/10.1093/carcin/bgp084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19372141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19372141"}]}]}]}