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.
Mohrs
M
M
Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA.
Blankespoor
C M
CM
Wang
Z E
ZE
Loots
G G
GG
Afzal
V
V
Hadeiba
H
H
Shinkai
K
K
Rubin
E M
EM
Locksley
R M
RM
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*
D016207:Cytokines; D021901:DNA, Intergenic; D012333:RNA, Messenger; D015847:Interleukin-4