Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system

Nippostrongylus brasiliensis infection and ovalbumin-induced allergic lung pathology are highly interleukin (IL)-4/IL-13 dependent, but the contributions of IL-4/IL-13 from adaptive (T helper [Th]2 cells) and innate (eosinophil, basophils, and mast cells) immune cells remain unknown. Although required for immunoglobulin (Ig)E induction, IL-4/IL-13 from Th2 cells was not required for worm expulsion, tissue inflammation, or airway hyperreactivity. In contrast, innate hematopoietic cell–derived IL-4/IL-13 was dispensable for Th2 cell differentiation in lymph nodes but required for effector cell recruitment and tissue responses. Eosinophils were not required for primary immune responses. Thus, components of type 2 immunity mediated by IL-4/IL-13 are partitioned between T cell–dependent IgE and an innate non-eosinophil tissue component, suggesting new strategies for interventions in allergic immunity.

[1]  Markus Mohrs,et al.  Activation of the integrated stress response during T helper cell differentiation , 2006, Nature Immunology.

[2]  C. Potten,et al.  Accelerated Intestinal Epithelial Cell Turnover: A New Mechanism of Parasite Expulsion , 2005, Science.

[3]  F. Finkelman,et al.  IL-2 and Autocrine IL-4 Drive the In Vivo Development of Antigen-Specific Th2 T Cells Elicited by Nematode Parasites12 , 2005, The Journal of Immunology.

[4]  A. Gessner,et al.  Mast Cells, Basophils, and Eosinophils Acquire Constitutive IL-4 and IL-13 Transcripts during Lineage Differentiation That Are Sufficient for Rapid Cytokine Production1 , 2005, The Journal of Immunology.

[5]  M. Wills-Karp,et al.  Interleukin‐13 in asthma pathogenesis , 2004, Immunological reviews.

[6]  F. Finkelman,et al.  Basophils Initiate IL-4 Production during a Memory T-dependent Response , 2004, The Journal of experimental medicine.

[7]  F. Finkelman,et al.  Interleukin‐4‐ and interleukin‐13‐mediated host protection against intestinal nematode parasites , 2004, Immunological reviews.

[8]  W. Paul,et al.  Basophils Produce IL-4 and Accumulate in Tissues after Infection with a Th2-inducing Parasite , 2004, The Journal of experimental medicine.

[9]  D. Voehringer,et al.  Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. , 2004, Immunity.

[10]  R. Star,et al.  Peripheral CD4 T Cells Rapidly Accumulate at the Host:Parasite Interface during an Inflammatory Th2 Memory Response1 , 2004, The Journal of Immunology.

[11]  T. Nutman,et al.  Parasite Antigen-Driven Basophils Are a Major Source of IL-4 in Human Filarial Infections , 2004, The Journal of Immunology.

[12]  E. Raz,et al.  Accumulation of Peribronchial Mast Cells in a Mouse Model of Ovalbumin Allergen Induced Chronic Airway Inflammation: Modulation by Immunostimulatory DNA Sequences1 , 2003, The Journal of Immunology.

[13]  L. Shultz,et al.  T Cells Are Required for Host Protection against Brugia malayi but Need Not Produce or Respond to Interleukin-4 , 2003, Infection and Immunity.

[14]  G. Pavlath,et al.  IL-4 Acts as a Myoblast Recruitment Factor during Mammalian Muscle Growth , 2003, Cell.

[15]  M. Wills-Karp,et al.  Interleukin-13 in asthma , 2003, Current opinion in pulmonary medicine.

[16]  K. Toellner,et al.  Th2 Activities Induced During Virgin T Cell Priming in the Absence of IL-4, IL-13, and B Cells1 , 2002, The Journal of Immunology.

[17]  D. Sheppard,et al.  Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma , 2002, Nature Medicine.

[18]  S. Orkin,et al.  Targeted Deletion of a High-Affinity GATA-binding Site in the GATA-1 Promoter Leads to Selective Loss of the Eosinophil Lineage In Vivo , 2002, The Journal of experimental medicine.

[19]  I. Pavord,et al.  Mast-cell infiltration of airway smooth muscle in asthma. , 2002, The New England journal of medicine.

[20]  F. Finkelman,et al.  Cutting Edge: IL-4 Receptor Expression by Non-Bone Marrow-Derived Cells Is Required to Expel Gastrointestinal Nematode Parasites1 , 2001, The Journal of Immunology.

[21]  J. Oliver,et al.  Immunohistochemical detection of human basophils in postmortem cases of fatal asthma. , 2001, American journal of respiratory and critical care medicine.

[22]  R. Locksley,et al.  Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter. , 2001, Immunity.

[23]  J. Schroeder,et al.  IL-4 production by human basophils found in the lung following segmental allergen challenge. , 2001, Journal of Allergy and Clinical Immunology.

[24]  W. Paul,et al.  Conventional, Naive CD4+ T Cells Provide an Initial Source of IL-4 During Th2 Differentiation , 2000, The Journal of Immunology.

[25]  S. Collins,et al.  Interleukin‐5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infections , 2000, Parasite immunology.

[26]  A. Sher,et al.  Single Cell Analysis Reveals That IL-4 Receptor/Stat6 Signaling Is Not Required for the In Vivo or In Vitro Development of CD4+ Lymphocytes with a Th2 Cytokine Profile , 2000, The Journal of Immunology.

[27]  A. Balic,et al.  Do eosinophils have a role in the killing of helminth parasites? , 2000, Parasitology today.

[28]  F. Finkelman,et al.  Stat6 Regulation of In Vivo IL-4 Responses1 , 2000, The Journal of Immunology.

[29]  G. Mayrhofer,et al.  Trapping and Immobilization ofNippostrongylus brasiliensis Larvae at the Site of Inoculation in Primary Infections of Interleukin-5 Transgenic Mice , 1999, Infection and Immunity.

[30]  C. Benoist,et al.  Mice lacking all conventional MHC class II genes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  G. McKenzie,et al.  Simultaneous Disruption of Interleukin (IL)-4 and IL-13 Defines Individual Roles in T Helper Cell Type 2–mediated Responses , 1999, The Journal of experimental medicine.

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

[33]  Andreas Bohne,et al.  PDB2MultiGIF: A Web Tool to Create Animated Images of Molecules , 1998 .

[34]  F. Brombacher,et al.  Differences between IL-4Rα-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses , 1998, Current Biology.

[35]  R. Locksley,et al.  Requirements for Allergen-Induced Airway Hyperreactivity in T and B Cell-Deficient Mice , 1998, Molecular medicine.

[36]  W. Paul,et al.  An interleukin 4 (IL-4)-independent pathway for CD4+ T cell IL-4 production is revealed in IL-4 receptor-deficient mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[37]  R. Coffman,et al.  Multiple Pathways for the Initiation of T Helper 2 (Th2) Responses , 1997, The Journal of experimental medicine.

[38]  M. Horton,et al.  Expression of IL-5 in thymocytes/T cells leads to the development of a massive eosinophilia, extramedullary eosinophilopoiesis, and unique histopathologies. , 1997, Journal of immunology.

[39]  K. Takatsu,et al.  Protective roles of eosinophils in Nippostrongylus brasiliensis infection. , 1997, International archives of allergy and immunology.

[40]  J. Kinoshita.  Women Fight Uphill Battle for Equity , 1996, Science.

[41]  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.

[42]  R. Locksley,et al.  The Instructive Role of Innate Immunity in the Acquired Immune Response , 1996, Science.

[43]  M. Kaplan,et al.  Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. , 1996, Immunity.

[44]  F. Finkelman,et al.  IL-4 treatment can cure established gastrointestinal nematode infections in immunocompetent and immunodeficient mice. , 1995, Journal of immunology.

[45]  Santa Jeremy Ono,et al.  Secretion of IL-4 from human basophils. The relationship between IL-4 mRNA and protein in resting and stimulated basophils. , 1994, Journal of immunology.

[46]  T. Koshino,et al.  Identification of basophils by immunohistochemistry in the airways of post‐mortem cases of fatal asthma , 1993, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[47]  S. Tonegawa,et al.  Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stages , 1992, Nature.

[48]  M. Rudnicki,et al.  Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. , 1992, Nature.

[49]  A. Heimberger,et al.  Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. , 1990, Science.

[50]  C. Parish,et al.  New fluorescent dyes for lymphocyte migration studies. Analysis by flow cytometry and fluorescence microscopy. , 1990, Journal of immunological methods.

[51]  F. Finkelman,et al.  The role of L3T4+ and Lyt-2+ T cells in the IgE response and immunity to Nippostrongylus brasiliensis. , 1988, Journal of immunology.

[52]  L. Mitchell,et al.  Kinetics of expulsion of the nematode, Nippostrongylus brasiliensis, in mast‐cell deficient W/Wv mice , 1983, Parasite immunology.

[53]  M. Vadas,et al.  Enhanced helminthotoxic capacity of eosinophils from patients with eosinophilia. , 1980, The New England journal of medicine.

[54]  D. McLaren,et al.  Complement-mediated killing of schistosomula of Schistosoma mansoni by rat eosinophils in vitro , 1978, The Journal of experimental medicine.

[55]  R. H. Jacobson,et al.  Expulsion of Nippostrongylus brasiliensis from mice lacking antibody production potential. , 1977, Immunology.