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 similar to 400.bp noncoding sequence in the intergenic region between the genes Il4 and III3, designated conserved noncoding sequence I (CNS-1), was deleted in mice. The capacity to develop T(H)2 cells was compromised in vit ro and in vivo in the absence of CNS-1. Despite the profound effect in T ce lls, mast cells from CNS-1(-/-) mice maintained their capacity to produce i nterleukin 4. AT cell-specific element critical for the optimal expression of type 2 cytokines may represent the evolution of a regulatory sequence ex ploited by adaptive immunity.