title: Deletion of a coordinate regulator of type 2 cytokine expression in mice.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mohrs
authors.forename: C M
authors.initials: CM
authors.lastname: Blankespoor
authors.forename: Z E
authors.initials: ZE
authors.lastname: Wang
authors.forename: G G
authors.initials: GG
authors.lastname: Loots
authors.forename: V
authors.initials: V
authors.lastname: Afzal
authors.forename: H
authors.initials: H
authors.lastname: Hadeiba
authors.forename: K
authors.initials: K
authors.lastname: Shinkai
authors.forename: E M
authors.initials: EM
authors.lastname: Rubin
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology; D002478:Cells, Cultured; D017124:Conserved Sequence; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D017384:Sequence Deletion; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D021901:DNA, Intergenic; D012333:RNA, Messenger; D015847:Interleukin-4