4.6 Article

IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans syndrome

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JOURNAL OF IMMUNOLOGY
卷 178, 期 1, 页码 511-519

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AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.1.511

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资金

  1. NCI NIH HHS [P50CA90388, CA87879] Funding Source: Medline
  2. NHLBI NIH HHS [HL66027, HL080206, P50HL67665, HL086491, HL087186] Funding Source: Medline
  3. NIAMS NIH HHS [AR055075] Funding Source: Medline
  4. NATIONAL CANCER INSTITUTE [R01CA087879, P50CA090388] Funding Source: NIH RePORTER
  5. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL066027, P50HL067665, R01HL080206] Funding Source: NIH RePORTER
  6. NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR055075] Funding Source: NIH RePORTER

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Acute allograft rejection is considered to be a predominately type 1 immune mediated response to the donor alloantigen. However, the type 2 immune mediated response has been implicated in multiple fibroproliferative diseases. Based on the fibro-obliterative lesion found during bronchiolitis obliterans syndrome (BOS), we hypothesized that the type 2 immune mediated response is involved in chronic lung allograft rejection. Specifically, whereas acute rejection is, in part, a type 1 immune response, chronic rejection is, in part, a type 2 immune response. We found the type 2 cytokine, IL-13, to be elevated and biologically active in human bronchoalveolar lavage fluid during BOS. Translational studies using a murine model of BOS demonstrated increased expression of IL-13 and its receptors that paralleled fibro-obliteration. In addition, in vivo neutralization of IL-13 reduced airway allograft matrix deposition and murine BOS, by a mechanism that was independent of IL-4. Furthermore, using IL-13R alpha 2(-/-) mice, we found increased fibro-obliteration. Moreover, anti-IL-13 therapy in combination with cyclosporin A had profound effects on reducing murine BOS. This supports the notion that IL-13 biological axis plays an important role during the pathogenesis of BOS independent of the IL-4 biological axis.

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