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

Nature Immunology volume 2, pages 842–847 (2001)Cite this article

Abstract

Mechanisms that underlie the patterning of cytokine expression in T helper (TH) cell subsets remain incompletely defined. An evolutionarily conserved ∼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 TH2 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.

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Figure 1: Generation of CNS-1−/− mice.
Figure 2: Cytokine expression in vitro by CNS-1−/− CD4+ T cells.
Figure 3: Amounts of IL-4 mRNA in CNS-1−/− CD4+ T cells.
Figure 4: Numbers of IL-4–expressing mast cells are not altered by the absence of CNS-1.
Figure 5: Baseline serum IgE concentration correlated inversely with the presence of CNS-1.
Figure 6: Impaired TH2 development in N. brasiliensis–infected CNS-1−/− mice.
Figure 7: Impaired TH2 development in CNS-1−/− mice after A. fumigatus–induced allergic airways disease.
Figure 8: Impaired TH2 development in CNS-1−/− mice after L. major infection.

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Acknowledgements

We thank C. McArthur, N. Flores and L. Stowring for technical assistance and E. Levine for statistical analysis. Animals were used in accordance with UCSF and UCB guidelines. Supported by grants NIH AI30663, HL56385 and HL66671. K. S. is supported by NIH-NIGMS-MSTP GM07618 UCSF.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, University of California San Francisco, San Francisco, 94143, CA, USA

    Markus Mohrs, Zhi-En Wang & Richard M. Locksley

  2. Departments of Medicine and Microbiology-Immunology, University of California San Francisco, San Francisco, 94143, CA, USA

    Markus Mohrs, Husein Hadeiba, Kanade Shinkai & Richard M. Locksley

  3. Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, 94720, CA, USA

    Catherine M. Blankespoor, Gaby G. Loots, Veena Afzal & Edward M. Rubin

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Correspondence to Richard M. Locksley.

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Mohrs, M., Blankespoor, C., Wang, ZE. et al. Deletion of a coordinate regulator of type 2 cytokine expression in mice. Nat Immunol 2, 842–847 (2001). https://doi.org/10.1038/ni0901-842

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