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

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.

Pubmed ID: 11526400

Authors

  • Mohrs M
  • Blankespoor CM
  • Wang ZE
  • Loots GG
  • Afzal V
  • Hadeiba H
  • Shinkai K
  • Rubin EM
  • Locksley RM

Journal

Nature immunology

Publication Data

September 29, 2001

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI30663
  • Agency: NIGMS NIH HHS, Id: GM07618
  • Agency: NHLBI NIH HHS, Id: HL56385
  • Agency: NHLBI NIH HHS, Id: HL66671

Mesh Terms

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