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

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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