Abstract
The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways 1 , how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells—integrin β7 + natural gut intraepithelial T lymphocytes (natural IELs)—that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin β7 − mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-1 2 , which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.
| Original language | English |
|---|---|
| Pages (from-to) | 115-119 |
| Number of pages | 5 |
| Journal | Nature |
| Volume | 566 |
| Issue number | 7742 |
| DOIs | |
| Publication status | Published - 2019 Feb 7 |
| Externally published | Yes |
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Cite this
Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease. / He, Shun; Kahles, Florian; Rattik, Sara; Nairz, Manfred; McAlpine, Cameron S.; Anzai, Atsushi; Selgrade, Daniel; Fenn, Ashley M.; Chan, Christopher T.; Mindur, John E.; Valet, Colin; Poller, Wolfram C.; Halle, Lennard; Rotllan, Noemi; Iwamoto, Yoshiko; Wojtkiewicz, Gregory R.; Weissleder, Ralph; Libby, Peter; Fernández-Hernando, Carlos; Drucker, Daniel J.; Nahrendorf, Matthias; Swirski, Filip K.
In: Nature, Vol. 566, No. 7742, 07.02.2019, p. 115-119.Research output: Contribution to journal › Letter
}
TY - JOUR
T1 - Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease
AU - He, Shun
AU - Kahles, Florian
AU - Rattik, Sara
AU - Nairz, Manfred
AU - McAlpine, Cameron S.
AU - Anzai, Atsushi
AU - Selgrade, Daniel
AU - Fenn, Ashley M.
AU - Chan, Christopher T.
AU - Mindur, John E.
AU - Valet, Colin
AU - Poller, Wolfram C.
AU - Halle, Lennard
AU - Rotllan, Noemi
AU - Iwamoto, Yoshiko
AU - Wojtkiewicz, Gregory R.
AU - Weissleder, Ralph
AU - Libby, Peter
AU - Fernández-Hernando, Carlos
AU - Drucker, Daniel J.
AU - Nahrendorf, Matthias
AU - Swirski, Filip K.
PY - 2019/2/7
Y1 - 2019/2/7
N2 - The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways 1 , how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells—integrin β7 + natural gut intraepithelial T lymphocytes (natural IELs)—that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin β7 − mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-1 2 , which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.
AB - The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways 1 , how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells—integrin β7 + natural gut intraepithelial T lymphocytes (natural IELs)—that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin β7 − mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-1 2 , which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.
UR - http://www.scopus.com/inward/record.url?scp=85060997991&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060997991&partnerID=8YFLogxK
U2 - 10.1038/s41586-018-0849-9
DO - 10.1038/s41586-018-0849-9
M3 - Letter
C2 - 30700910
AN - SCOPUS:85060997991
VL - 566
SP - 115
EP - 119
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 7742
ER -