Human eosinophils express and release IL‐13 following CD28‐dependent activation

Human eosinophils produce a large number of cytokines, including immunoregulatory cytokines. Given that eosinophils store and release interleukin (IL)‐4, a key cytokine in the pathogenesis of allergic inflammation, and that IL‐4 and IL‐13 share common biological functions, we investigated the possibility that IL‐13 may be synthesized by these cells. Using flow cytometry and immunocytochemistry, we show that eosinophils synthesize and store IL‐13. Granule localization was demonstrated after subcellular fractionation, and IL‐13 immunoreactivity was localized to crystalloid, granule‐enriched fractions. Furthermore, electron microscopic analyses specifically localized IL‐13 to the dense cores of bicompartmental secondary granules. Upon CD28 ligation, IL‐13 was released by eosinophils, whereas a combination of CD28 and immunoglobulin A complexes resulted in decreased IL‐13 secretion. Furthermore, eosinophil‐derived IL‐13 exerts a biological effect, inducing CD23 expression on B cells. By having the capacity to synthesize and release IL‐13, eosinophils may participate in the development and maintenance of the T helper cell type 2 response, a prominent feature of allergic diseases.

[1]  D. Dombrowicz,et al.  Human Eosinophils and Human High Affinity IgE Receptor Transgenic Mouse Eosinophils Express Low Levels of High Affinity IgE Receptor, but Release IL-10 upon Receptor Activation , 2001, The Journal of Immunology.

[2]  L. J. Woods,et al.  Cutting Edge: Eotaxin Elicits Rapid Vesicular Transport-Mediated Release of Preformed IL-4 from Human Eosinophils1 , 2001, The Journal of Immunology.

[3]  F. Levi-Schaffer,et al.  Human peripheral blood eosinophils express stem cell factor. , 2001, Blood.

[4]  Paige Lacy,et al.  Immune effector functions of eosinophils in allergic airway inflammation , 2001, Current opinion in allergy and clinical immunology.

[5]  A. Herbelin,et al.  CD11c+ Eosinophils in the Murine Thymus: Developmental Regulation and Recruitment upon MHC Class I-Restricted Thymocyte Deletion , 2000, The Journal of Immunology.

[6]  A. Dvorak,et al.  Ultrastructural analysis of human eosinophils. , 2000, Chemical immunology.

[7]  M. Capron,et al.  IL‐4 production by human polymorphonuclear neutrophils , 2000, Journal of leukocyte biology.

[8]  F. Symon,et al.  Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow. , 2000, Blood.

[9]  P. Weller,et al.  Lymph node trafficking and antigen presentation by endobronchial eosinophils. , 2000, The Journal of clinical investigation.

[10]  Hirai,et al.  Interleukin‐13 and tumour necrosis factor‐α synergistically induce eotaxin production in human nasal fibroblasts , 2000, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[11]  G. McKenzie,et al.  Schistosome Infection of Transgenic Mice Defines Distinct and Contrasting Pathogenic Roles for IL-4 and IL-13: IL-13 Is a Profibrotic Agent1 , 2000, The Journal of Immunology.

[12]  Paige Lacy,et al.  Eosinophil cytokines. , 2000, Chemical immunology.

[13]  A. Capron,et al.  Expression of Cd28 and Cd86 by Human Eosinophils and Role in the Secretion of Type 1 Cytokines (Interleukin 2 and Interferon γ) , 1999, The Journal of experimental medicine.

[14]  Paige Lacy,et al.  Rapid mobilization of intracellularly stored RANTES in response to interferon-gamma in human eosinophils. , 1999, Blood.

[15]  T. Mosmann,et al.  Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. , 1999, Journal of immunology.

[16]  T. Wynn,et al.  IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs. , 1999, Journal of immunology.

[17]  D B Corry,et al.  Requirement for IL-13 independently of IL-4 in experimental asthma. , 1998, Science.

[18]  D D Donaldson,et al.  Interleukin-13: central mediator of allergic asthma , 1998 .

[19]  R. Pawankar,et al.  Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking: enhanced IL-13 production by IL-4-primed human mast cells. , 1998, The Journal of allergy and clinical immunology.

[20]  J. Vries.  The role of IL-13 and its receptor in allergy and inflammatory responses , 1998 .

[21]  F. Levi-Schaffer,et al.  Intracellular localization of interleukin-6 in eosinophils from atopic asthmatics and effects of interferon gamma. , 1998, Blood.

[22]  C Caux,et al.  The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. , 1998, Journal of immunology.

[23]  J. Banchereau,et al.  Interleukin-4 and interleukin-13: their similarities and discrepancies. , 1998, International reviews of immunology.

[24]  J. D. de Vries.  The role of IL-13 and its receptor in allergy and inflammatory responses. , 1998, The Journal of allergy and clinical immunology.

[25]  J. D. de Vries,et al.  The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells. , 1997, The Journal of allergy and clinical immunology.

[26]  A. Minty,et al.  The related cytokines interleukin-13 and interleukin-4 are distinguished by differential production and differential effects on T lymphocytes. , 1997, European cytokine network.

[27]  J. Bonnefoy,et al.  Structure and functions of CD23. , 1997, International reviews of immunology.

[28]  J. Butterfield,et al.  Human lung mast cell activation leads to IL-13 mRNA expression and protein release. , 1996, American journal of respiratory cell and molecular biology.

[29]  Franco H Falcone,et al.  Purified human peripheral blood basophils release interleukin‐13 and preformed interleukin‐4 following immunological activation , 1996, European journal of immunology.

[30]  W. Luttmann,et al.  Activation of human eosinophils by IL-13. Induction of CD69 surface antigen, its relationship to messenger RNA expression, and promotion of cellular viability. , 1996, Journal of immunology.

[31]  R. Alam,et al.  IL-13 released by and localized in human basophils. , 1996, Journal of immunology.

[32]  H. Kita,et al.  Constitutive production of IL-4 and IL-10 and stimulated production of IL-8 by normal peripheral blood eosinophils. , 1996, Journal of immunology.

[33]  J. Calafat,et al.  Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes. , 1996, Blood.

[34]  L. Boulet,et al.  Gene expression of interleukin-2 in purified human peripheral blood eosinophils. , 1996, Immunology.

[35]  F. Levi-Schaffer,et al.  Identification of interleukin-2 in human peripheral blood eosinophils. , 1996, Immunology.

[36]  S. Durham,et al.  Identification of messenger RNA for IL-4 in human eosinophils with granule localization and release of the translated product. , 1995, Journal of immunology.

[37]  P. O'Byrne,et al.  Distinct immunohistochemical localization of IL-4 in human inflamed airway tissues. IL-4 is localized to eosinophils in vivo and is released by peripheral blood eosinophils. , 1995, Journal of immunology.

[38]  F. Mills,et al.  Activated mast cells produce interleukin 13 , 1995, The Journal of experimental medicine.

[39]  R. Coffman,et al.  IL-13 selectively induces vascular cell adhesion molecule-1 expression in human endothelial cells. , 1995, Journal of immunology.

[40]  J. Tavernier,et al.  Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion , 1994, The Journal of experimental medicine.

[41]  A. Minty,et al.  Interleukin 13 is a B cell stimulating factor , 1994, The Journal of experimental medicine.

[42]  J. D. de Vries,et al.  Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. , 1994, Immunology today.

[43]  R. Coffman,et al.  Modulation of murine macrophage function by IL-13. , 1993, Journal of immunology.

[44]  C. Figdor,et al.  Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. , 1993, Journal of immunology.

[45]  R. de Waal Malefyt,et al.  Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[46]  R. de Waal Malefyt,et al.  Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Capron,et al.  Interleukin 5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease , 1992, The Journal of experimental medicine.