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Role of IL-5 in Immune and Pathological Responses in the Mouse

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Book cover Cytokine Knockouts

Part of the book series: Contemporary Immunology ((CONTIM))

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Summary

Studies in interleukin (IL)-5-/- mice have shown that this cytokine plays a critical role in the regulation of eosinophil expansion in the bone marrow and blood in response to allergic and parasitic stimuli. IL-5 also plays a central role in regulating baseline blood and tissue eosinophil numbers but is not essential for eosinophil development or migration. Thus, eosinophil accumulation into allergic tissues should not be viewed as a process that is exclusively regulated by IL-5, but one that is greatly enhanced by this cytokine. Although IL-5 regulated eosinophilia plays an important role in the regulation of allergic inflammation and the subsequent development of disease, its role in the elimination of parasites and in nonallergic disease processes is less clear. This may stem from the observation that eosinophils can accumulate in tissues independently of IL-5 and that these alternative pathways coexist in many disease and immune responses. Importantly, studies in IL-5-/- mice are disclosing an important role for this cytokine in the regulation of immune responses by modulating lymphocyte function.

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References

  1. Kopf, M., Brombacher, F., Hodgkin, P. D., et al. (1996) IL-S-deficient mice have a developmental defect in CDS+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity 4, 15–24.

    Article  PubMed  CAS  Google Scholar 

  2. Rothenberg, M. (1998) Eosinophilia. N. Engl. J. Med. 338, 1592–1600.

    Article  PubMed  CAS  Google Scholar 

  3. Weller, P. F. (1994) Eosinophils: structure and functions. Curr. Opin. Immunol. 6, 85–90.

    Article  PubMed  CAS  Google Scholar 

  4. Rothenberg, M. E., Mishra, A., Brandt, E. B., and Hogan, S. P. (2001) Gastrointestinal eosinophils in health and disease. Adv. Immunol. 78, 291–328.

    Article  PubMed  CAS  Google Scholar 

  5. Foster, P. S., Hogan, S. P., Ramsay A. J., Matthaei, K. I., and Young, I. G. (1996) Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model [see comments]. J. Exp. Med. 183, 195–201.

    Article  PubMed  CAS  Google Scholar 

  6. Wills-Karp, M. (1999) Immunologic basis of antigen-induced airway hyperresponsiveness. Annu. Rev. Immunol. 17, 255–281.

    Article  PubMed  CAS  Google Scholar 

  7. Wills-Karp, M. (2000) Murine models of asthma in understanding immune dysregulation in human asthma. Immunopharmacology 48, 263–268.

    Article  PubMed  CAS  Google Scholar 

  8. Robinson, D. S., Durham, S. R., and Kay, A. B. (1993) Cytokines in asthma. Thorax 48, 845–853.

    Article  PubMed  CAS  Google Scholar 

  9. Foster, P., Mould, A., Yang, M., et al. (2001) Elemental signals regulating eosinophil accumulation in the lung. Immunol. Rev. 179, 173–181.

    Article  PubMed  CAS  Google Scholar 

  10. Hogan, S. P., Matthaei, K. I., Young, J. M., Koskinen, A., Young, I. G., and Foster, P. S. (1998) A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5. J. Immunol. 161, 1501–1509.

    PubMed  CAS  Google Scholar 

  11. Hogan, S. P., Koskinen, A., Matthaei, K. I., Young, I. G., and Foster, P. S. (1998) Interleukin-5producing CD4+ T cells play a pivotal role in aeroallergen-induced eosinophilia, bronchial hyper-reactivity, and lung damage in mice. Am. J. Respir. Crit. Care Med. 157, 210–218.

    PubMed  CAS  Google Scholar 

  12. Hogan, S., Mishra, E., Brandt, E., Foster, P., and Rothenberg, M. (2000) A critical role for eotaxin in experimental arai antigen-indcued eosinophilic gastrointestinal allergy. Proc. Natl. Acad. Sci. 97, 6681–6686.

    Article  PubMed  CAS  Google Scholar 

  13. Mattes, J., Yang, M., Mahalingam, S., et al. (2002) Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma. J. Exp. Med. 195, 1433–1444.

    Article  PubMed  CAS  Google Scholar 

  14. Mould, A. W., Ramsay, A. J., Matthaei, K. I., Young, I. G., Rothenberg, M. E., and Foster, P. S. (1999) Role of IL-5, eotaxin, and T-lymphocytes in regulating eosinophil trafficking, degranula-tion, and airways hyperreactivity. submitted.

    Google Scholar 

  15. Mould, A. W., Ramsay, A. J., Matthaei, K. I., Young, I. G., Rothenberg, M. E., and Foster, P. S. (2000) The effect of IL-5 and eotaxin expression in the lung on eosinophil trafficking and degranulation and the induction of bronchial hyperreactivity. J. Immunol. 164, 2142–2150.

    PubMed  CAS  Google Scholar 

  16. Sanderson, C. J., Campbell, H. D., and Young, I. G. (1988) Molecular and cellular biology of eosinophil differentiation factor (interleukin-5) and its effects on human and mouse B cells. Immunol. Rev. 102, 29–50.

    Article  PubMed  CAS  Google Scholar 

  17. Nishinakamura, R., Miyajima, A., Mee, P. J., Tybulewicz, V. L. J., and Murray, R. (1996) Hematopoiesis in mice lacking the entire granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 functions. Blood 88, 2458–2464.

    PubMed  CAS  Google Scholar 

  18. Foster, P., Hogan, S., Ramsay, A., Matthaei, K., and Young, I. (1996) Interleukin-5 deficiency abolishes eosinophilia, airway hyperreactivity and lung damage in mouse asthma model. J. Exp. Med. 183, 195–201.

    Article  PubMed  CAS  Google Scholar 

  19. Takamoto, M., Ovington, K. S., Behm, C. A., Sugane, K., Young, I. G., and Matthaei, K. I. (1997) Eosinophilia, parasite burden and lung damage in Toxocara canis infection in C57B1/6 mice genetically deficient in IL-5. Immunology 90, 511–517.

    Article  PubMed  CAS  Google Scholar 

  20. Robertson, S. A., Mau, V. J., Young, I. G., and Matthaei, K. I. (2000) Uterine eosinophils and reproductive performance in interleukin 5-deficient mice. J. Rep rod. Fertil. 120, 423–432.

    CAS  Google Scholar 

  21. Wang, J., Palmer, K., Lotvall, J., et al. (1998) Circulating, but not local lung, IL-5 is required for the development of antigen-induced airways eosinophilia. J. Clin. Invest. 102, 1132–1141.

    Article  PubMed  CAS  Google Scholar 

  22. Coyle, A. J., Kohler, G., Tsuyuki, S., Brombacher, F., and Kopf, M. (1998) Eosinophils are not required to induce airway hyperresponsiveness after nematode infection. Eur. J. Immunol. 28, 2640–2647.

    Article  PubMed  CAS  Google Scholar 

  23. Temelkovski, J., Hogan, S. P., Shepherd, D. P., Foster, P. S., and Kumar, R. K. (1998) An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen. Thorax 53, 849–856.

    Article  PubMed  CAS  Google Scholar 

  24. Foster, P. S., Ming, Y., Matthei, K. I., Young, I. G., Temelkovski, J., and Kumar, R. K. (2000) Dissociation of inflammatory and epithelial responses in a murine model of chronic asthma. Lab. Invest. 80, 655–662.

    Article  PubMed  CAS  Google Scholar 

  25. Saito, H., Matsumoto, K., Denburg, A. E., et al. (2002) Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency. J. Immunol. 168, 3017–3023.

    PubMed  CAS  Google Scholar 

  26. Spergel, J. M., Mizoguchi, E., Oettgen, H., Bhan, A. K., and Geha, R. S. (1999) Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J. Clin. Invest. 103, 1103–1111.

    Article  PubMed  CAS  Google Scholar 

  27. Hogan, S. P., Mishra, A., Brandt, E. B., et al. (2001) A pathological role for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat. Immunol. 2, 353–360.

    Article  PubMed  CAS  Google Scholar 

  28. Hogan, S. P., Foster, P. S., and Rothenberg, M. E. (2002) Experimental analysis of eosinophilassociated gastrointestinal diseases. Curr. Opin. Allergy Clin. Immunol. 2, 239–248.

    Article  PubMed  Google Scholar 

  29. Mishra, A., Hogan, S. P., Lee, J. J., Foster, P. S., and Rothenberg, M. E. (1999) Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J. Clin. Invest. 103, 1719–1727.

    Article  PubMed  CAS  Google Scholar 

  30. Mishra, A., Hogan, S. P., Brandt, E. B., and Rothenberg, M. E. (2000) Peyer’s patch eosinophils: identification, characterization, and regulation by mucosal allergen exposure, interleukin-5, and eotaxin. Blood 96. 1538–1544.

    PubMed  CAS  Google Scholar 

  31. Mishra, A., Hogan, S. P., Brandt, E. B., and Rothenberg, M. E. (2001) An etiological role for aeroallergens and eosinophils in experimental esophagitis. J. Clin. Invest. 107, 83–90.

    Article  PubMed  CAS  Google Scholar 

  32. Mishra, A., Hogan, S. P., Brandt, E. B., et al. (2001) Enterocyte expression of the eotaxin and IL-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. J. Biol. Chem. 30, 30.

    Google Scholar 

  33. Mishra, A., Hogan, S. P., and Rothenberg, M. E. (2002) Interleukin-5 promotes eosinophil trafficking to the esophagus. J. Immunol. 5, 2464–2469.

    Google Scholar 

  34. Rothenberg, M. E., Mishra, A., Brandt, E. B., and Hogan, S. P. (2001) Gastrointestinal eosinophils. Immunol. Rev. 179, 139–155.

    Article  PubMed  CAS  Google Scholar 

  35. Brunet, L. R., Sabin, E. A., Cheever, A. W., Kopf, M. A., and Pearce, E. J. (1999) Interleukin 5 (IL-5) is not required for expression of a Th2 response or host resistance mechanisms during murine Schistosoma mansoni but does play a role in development of IL-4-producing non-T, non-B cells. Infect. Immun. 67, 3014–3018.

    PubMed  CAS  Google Scholar 

  36. Sabin, E. A., Kopf, M. A., and Pearce, E. J. (1996) Schistosoma mansoni egg-induced early IL-4 production is dependent upon IL-5 and eosinophils. J. Exp. Med. 184, 1871–1878.

    Article  PubMed  CAS  Google Scholar 

  37. Valiance, B. A., Blennerhassett, P. A., Deng, Y., Matthaei, K. I., Young, I. G., and Collins, S. M. (1999) IL-5 contributes to worm expulsion and muscle hypercontractility in a primary T. spiralis infection. Am. J. Physiol. 277, G400 - G408.

    Google Scholar 

  38. Vallance, B. A., Matthaei, K. I., Sanovic, S., Young, I. G., and Collins, S. M. (2000) Interleukin-5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infections. Parasite Immunol. 22, 487–492.

    Article  PubMed  CAS  Google Scholar 

  39. Ovington, K. S., McKie, K., Matthaei, K. I., Young, I. G., and Behm, C. A. (1998) Regulation of primary Strongyloides ratti infections in mice: a role for interleukin-5. Immunology 95, 488–493.

    Article  PubMed  CAS  Google Scholar 

  40. Nickdei, M. B., Roberts, F., Brombacher, F., Alexander, J., and Roberts, C. W. (2001) Counter-protective role for interleukin-5 during acute Toxoplasma gondii infection. Infect. Immun. 69, 1044–1052.

    Article  Google Scholar 

  41. Zhang, Y., and Denkers, E. Y. (1999) Protective role for interleukin-5 during chronic Toxoplasma gondii infection. Infect. Immun. 67, 4383–4392.

    PubMed  CAS  Google Scholar 

  42. Simeonovic, C. J., Townsend, M. J., Wilson, J. D., et al. (1997) Eosinophils are not required for the rejection of neovascularized fetal pig proislet xenografts in mice. J. Immunol. 158, 2490–2499.

    PubMed  CAS  Google Scholar 

  43. Surquin, M., Le Moine, A., Flamand, V., et al. (2002) Skin graft rejection elicited by beta 2microglobulin as a minor transplantation antigen involves multiple effector pathways: role of Fas-Fas ligand interactions and Th2-dependent graft eosinophil infiltrates. J. Immunol. 169, 500–506.

    PubMed  CAS  Google Scholar 

  44. Stevceva, L., Pavli, P., Husband, A., Matthaei, K. I., Young, I. G., and Doe, W. F. (2000) Eosinophilia is attenuated in experimental colitis induced in IL-5 deficient mice. Genes Immun. 1, 213–218.

    Article  PubMed  CAS  Google Scholar 

  45. Kinashi, T., Harada, N., Severinson, E., et al. (1986) Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II. Nature 324, 70–73.

    Article  PubMed  CAS  Google Scholar 

  46. Bao, S., Beagley, K. W., Murray, A. M., et al. (1998) Intestinal IgA plasma cells of the B1 lineage are IL-5 dependent. Immunology 94, 181–188.

    Article  PubMed  CAS  Google Scholar 

  47. Takatsu, K., Kikuchi, Y., Takahashi, T., et al. (1987) Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 84, 4234–4238.

    Article  PubMed  CAS  Google Scholar 

  48. Apostolopoulos, V., McKenzie, I. F., Lees, C., Matthaei, K. I., and Young, I. G. (2000) A role for IL-5 in the induction of cytotoxic T lymphocytes in vivo. Eur. J. Immunol. 30, 1733–1739.

    Article  PubMed  CAS  Google Scholar 

  49. MacKenzie, J. R., Mattes, J., Dent, L. A., and Foster, P. S. (2001) Eosinophils promote allergic disease of the lung by regulating CD4+ Th2 lymphocyte function. J. Immunol. 167, 3146–3155.

    PubMed  CAS  Google Scholar 

  50. Shi, H. Z., Humbles, A., Gerard, C., Jin, Z., and Weller, P. F. (2000) Lymph node trafficking and antigen presentation by endobronchial eosinophils. J. Clin. Invest. 105, 945–953.

    Article  PubMed  CAS  Google Scholar 

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Foster, P.S., Hogan, S.P. (2003). Role of IL-5 in Immune and Pathological Responses in the Mouse. In: Fantuzzi, G. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-405-4_12

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  • DOI: https://doi.org/10.1007/978-1-59259-405-4_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-415-9

  • Online ISBN: 978-1-59259-405-4

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