Carbonic anhydrase IV is expressed on IL-5-activated murine eosinophils

J Immunol. 2014 Jun 15;192(12):5481-9. doi: 10.4049/jimmunol.1302846. Epub 2014 May 7.


Eosinophilia and its cellular activation are hallmark features of asthma, as well as other allergic/Th2 disorders, yet there are few, if any, reliable surface markers of eosinophil activation. We have used a FACS-based genome-wide screening system to identify transcriptional alterations in murine lung eosinophils recruited and activated by pulmonary allergen exposure. Using a relatively stringent screen with false-positive correction, we identified 82 candidate genes that could serve as eosinophil activation markers and/or pathogenic effector markers in asthma. Carbonic anhydrase IV (Car4) was a top dysregulated gene with 36-fold induction in allergen-elicited pulmonary eosinophils, which was validated by quantitative PCR, immunohistochemistry, and flow cytometry. Eosinophil CAR4 expression was kinetically regulated by IL-5, but not IL-13. IL-5 was both necessary and sufficient for induction of eosinophil CAR4. Although CAR4-deficient mice did not have a defect in eosinophil recruitment to the lung, nor a change in eosinophil pH-buffering capacity, allergen-challenged chimeric mice that contained Car4(-/-) hematopoietic cells aberrantly expressed a series of genes enriched in biological processes involved in epithelial differentiation, keratinization, and anion exchange. In conclusion, we have determined that eosinophils express CAR4 following IL-5 or allergen exposure, and that CAR4 is involved in regulating the lung transcriptome associated with allergic airway inflammation; therefore, CAR4 has potential value for diagnosing and monitoring eosinophilic responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / genetics
  • Allergens / immunology
  • Animals
  • Asthma / diagnosis
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / pathology
  • Carbonic Anhydrase IV / biosynthesis
  • Carbonic Anhydrase IV / genetics
  • Carbonic Anhydrase IV / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Enzyme Induction / genetics
  • Enzyme Induction / immunology
  • Eosinophils / immunology*
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Hematopoietic Stem Cells
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Interleukin-5 / genetics
  • Interleukin-5 / immunology*
  • Interleukin-5 / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Knockout


  • Allergens
  • Interleukin-13
  • Interleukin-5
  • Carbonic Anhydrase IV
  • Car4 protein, mouse