Cylindromatosis (Cyld) gene mutation in T cells promotes the development of an IL-9-dependent allergic phenotype in experimental asthma

Cell Immunol. 2016 Oct;308:27-34. doi: 10.1016/j.cellimm.2016.06.003. Epub 2016 Jun 25.


Cylindromatosis (CYLD) is a ubiquitously expressed deubiquitinating enzyme which removes activating ubiquitin residues from important signaling molecules of the NF-κB pathway. In CYLDex7/8 transgenic mice, a naturally occurring short isoform (sCYLD) is overexpressed in the absence of full length CYLD, leading to excessive NF-κB activity. Herein, we investigated the impact of the CYLDex7/8 mutation selectively in T cells on the development of experimental allergic airway disease induced by sensitization and challenge with ovalbumin. Compared with their wildtype littermates, mice bearing the T cell-specific mutation (CD4+CYLDex7/8) display stronger eosinophilia and mucus production in the lungs and higher IgE serum levels. The reason for these observations is excessive production of T cell-derived IL-9, a cytokine to whom allergy-promoting properties were ascribed. Consequently, blockade of IL-9 in CD4+CYLDex7/8 mice alleviates the development of disease symptoms. Thus, by polarization of the T cell cytokine response, sCYLD can favor the development of allergic airway disease.

Keywords: Asthma; Cylindromatosis (turban tumor syndrome) gene; IL-9; Th9 cells.

MeSH terms

  • Animals
  • Asthma / genetics*
  • CD4-Positive T-Lymphocytes / physiology*
  • Deubiquitinating Enzyme CYLD
  • Eosinophils / physiology*
  • Humans
  • Hypersensitivity / genetics*
  • Interleukin-9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Mucus / metabolism
  • Mutation / genetics
  • Neoplastic Syndromes, Hereditary / genetics*
  • Skin Neoplasms / genetics*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • IL9 protein, human
  • Interleukin-9
  • Tumor Suppressor Proteins
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD

Supplementary concepts

  • Familial cylindromatosis