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Basophils and allergic inflammation

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1 Basophils and allergic inflammation
Mark C. Siracusa, PhD, Brian S. Kim, MD, Jonathan M. Spergel, MD, PhD, David Artis, PhD  Journal of Allergy and Clinical Immunology  Volume 132, Issue 4, Pages (October 2013) DOI: /j.jaci Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 The clinical relevance of basophils. Basophils have been shown to contribute to many human disease states, including allergic diseases (contact dermatitis, AD, hypersensitivity responses, and asthma), autoimmunity (bullous pemphigoid and lupus nephritis), inflammatory disorders (Crohn disease), and cancer (acute and chronic myelogenous leukemia). This article will focus on the contribution of basophils to allergic disease. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Basophil development. Murine basophils develop from HSC populations that reside in the bone marrow. As HSCs mature, they become GMPs, basophil mast cell precursors (BMCPs), and BaPs. To date, 2 cytokines, T cell–derived IL-3 and epithelial cell–derived TSLP, have been shown to promote distinct phases of basophil development. After fully maturing in the bone marrow, basophils can enter the periphery and contribute to inflammation. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Heterogeneous effector functions of basophil populations. Recent studies have demonstrated that IL-3–elicited basophils are highly responsive to FcεRI cross-linking through IgE-antigen complexes. After encountering antigen, IL-3–elicited basophils release multiple effector molecules that can contribute to allergic inflammation. TSLP-elicited basophils are nonresponsive to IgE-antigen complexes but produce multiple effector molecules after stimulation with cytokines, such as IL-33 and IL-18. The observed functional heterogeneity between IL-3–elicited and TSLP-elicited basophils might allow IL-3–elicited basophils and TSLP-elicited basophils to contribute to various allergic disorders that are associated with IgE responses, TSLP production, or both. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 The contributions of IgE and TSLP to allergic disease. Allergic disease states appear to separate into 3 separate categories: those that are highly IgE dependent (urticaria and food allergy), those that are partially IgE dependent (asthma and AD), and those that are IgE independent (eosinophilic esophagitis). Critically, allergic diseases that are only partially dependent on IgE or independent of IgE are highly associated with TSLP production. Therefore it is likely that IL-3–elicited basophils that are highly responsive to IgE-antigen complexes contribute to IgE-mediated allergic disorders, whereas TSLP-elicited basophils contribute to IgE-independent disorders. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions


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