Publication Date:
2013-11-10
Description:
Circadian clocks regulate numerous physiological processes that vary across the day-night (diurnal) cycle, but if and how the circadian clock regulates the adaptive immune system is mostly unclear. Interleukin-17-producing CD4(+) T helper (T(H)17) cells are proinflammatory immune cells that protect against bacterial and fungal infections at mucosal surfaces. Their lineage specification is regulated by the orphan nuclear receptor RORgammat. We show that the transcription factor NFIL3 suppresses T(H)17 cell development by directly binding and repressing the Rorgammat promoter. NFIL3 links T(H)17 cell development to the circadian clock network through the transcription factor REV-ERBalpha. Accordingly, TH17 lineage specification varies diurnally and is altered in Rev-erbalpha(-/-) mice. Light-cycle disruption elevated intestinal T(H)17 cell frequencies and increased susceptibility to inflammatory disease. Thus, lineage specification of a key immune cell is under direct circadian control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165400/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Xiaofei -- Rollins, Darcy -- Ruhn, Kelly A -- Stubblefield, Jeremy J -- Green, Carla B -- Kashiwada, Masaki -- Rothman, Paul B -- Takahashi, Joseph S -- Hooper, Lora V -- R01 DK070855/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):727-30. doi: 10.1126/science.1243884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24202171" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Basic-Leucine Zipper Transcription Factors/genetics/*metabolism
;
CLOCK Proteins/genetics
;
Cell Differentiation/*genetics
;
Cell Lineage/genetics
;
Circadian Clocks/genetics/*immunology
;
*Gene Expression Regulation
;
Germ-Free Life
;
HEK293 Cells
;
Humans
;
Intestine, Small/immunology/microbiology
;
Jurkat Cells
;
Mice
;
Mice, Inbred C57BL
;
Mice, Mutant Strains
;
Nuclear Receptor Subfamily 1, Group D, Member 1/genetics/metabolism
;
Nuclear Receptor Subfamily 1, Group F, Member 3/*genetics
;
Promoter Regions, Genetic
;
Th17 Cells/*cytology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
