Deletion of a coordinate regulator of type 2 cytokine expression in mice

Nat Immunol. 2001 Sep;2(9):842-7. doi: 10.1038/ni0901-842.


Mechanisms that underlie the patterning of cytokine expression in T helper (T(H)) cell subsets remain incompletely defined. An evolutionarily conserved approximately 400-bp noncoding sequence in the intergenic region between the genes Il4 and Il13, designated conserved noncoding sequence 1 (CNS-1), was deleted in mice. The capacity to develop T(H)2 cells was compromised in vitro and in vivo in the absence of CNS-1. Despite the profound effect in T cells, mast cells from CNS-1(-/-) mice maintained their capacity to produce interleukin 4. A T cell-specific element critical for the optimal expression of type 2 cytokines may represent the evolution of a regulatory sequence exploited by adaptive immunity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aspergillosis / immunology
  • Cells, Cultured
  • Conserved Sequence
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • DNA, Intergenic / genetics
  • DNA, Intergenic / physiology*
  • Gene Targeting
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Leishmaniasis, Cutaneous / immunology
  • Mast Cells / immunology
  • Mice
  • Mice, Knockout
  • RNA, Messenger / biosynthesis
  • Sequence Deletion
  • Strongylida Infections / immunology
  • Th2 Cells / immunology*


  • Cytokines
  • DNA, Intergenic
  • RNA, Messenger
  • Interleukin-4