Immune cell control of nutrient absorption

doi:10.1126/science.abg6455

GSTDTAP > 气候变化

DOI	10.1126/science.abg6455
	Immune cell control of nutrient absorption
	Jhimmy Talbot; Dan R. Littman
	2021-03-19
发表期刊	Science
出版年	2021
英文摘要	The gastrointestinal tract performs the critical function of nutrient acquisition, supplying the energetic and metabolic demands of most metazoan organisms. This process is subject to extensive regulation because of changes in nutrient availability and perturbations of the microbiota, as well as alterations in internal states such as depletion in nutrient stores, reproductive cues ([ 1 ][1]), and immune responses ([ 2 ][2]). The gastrointestinal system must thus have adaptive features that provide plasticity for its diverse functions. On page 1223 of this issue, Sullivan et al. ([ 3 ][3]) provide evidence that γδ T lymphocytes, immune cells that reside inside the intestine, are integral to a regulatory circuit that promotes local adaptation to increased abundance of sugars in the diet. This study could contribute to better insights into the association of alterated immune responses with metabolic disorders such as obesity and malabsorption syndromes. The transcriptional programs associated with absorptive and metabolic functions of the intestine can be altered by food intake and composition of the diet ([ 4 ][4], [ 5 ][5]). In the duodenum of mice fed with a sugar-rich diet, there is increased expression of genes associated with carbohydrate digestion and absorption ([ 5 ][5]). However, it was unclear how the increase in sugar content promotes changes in intestinal transcriptional programs that are associated with sugar metabolism [called the carbohydrate transcriptional program (CarbTP)]. Because of the extensive experimental evidence for a link between diet, the commensal microbiota, and host metabolism, Sullivan et al. examined the role of the host microbiome in controlling diet-dependent plasticity in CarbTP. However, a sugar-rich diet promoted up-regulation of the CarbTP in a microbiota-independent manner, providing evidence that not all intestinal metabolic alterations induced by dietary changes are controlled by the microbiota. The transport of nutrients from the intestinal lumen into the host is promoted by absorptive intestinal epithelial cells that, with their secreted mucins and other specialized epithelial cells, provide a physical barrier and are in direct contact with the ingested diet. The inability to recapitulate in vitro CarbTP increases through direct exposure of these epithelial cells to high amounts of sugar prompted Sullivan et al. to postulate that local adaptations to changes in diet composition may require more complex cellular interactions in the mouse intestine. They found that immune cells, and specifically γδ T lymphocytes, were important for up-regulation of the CarbTP in intestinal epithelial cells of mice fed a sugar-rich diet, compared with an isocaloric protein-rich diet. This places an immune cell at the center of a circuit that controls intestinal adaptation to the amount of macronutrients in the diet. ![Figure][6] Immune-mediated intestinal adaptation to dietary alterations A sugar-rich diet causes relocation of γδ T cells to the intestinal crypt, possibly through prostaglandin E2 (PGE2) signaling, where they inhibit interleukin-22 (IL-22) production by type 3 innate lymphoid cells (ILC3s). This leads to remodeling of epithelial cells and a transcriptional program associated with carbohydrate digestion and absorption (CarbTP). GRAPHIC: JOSHUA BIRD/ SCIENCE γδ T lymphocytes have distinct abilities to quickly respond to environmental perturbations and orchestrate immune responses. They straddle innate and adaptive immune functions and contribute not only to host antimicrobial defense but also to other physiological functions ([ 6 ][7]). Recent reports have revealed that γδ T lymphocytes can modulate neuronal functions and behavior ([ 7 ][8]), thermogenesis ([ 8 ][9]), and intestinal metabolism ([ 9 ][10]). γδ T lymphocytes in the intestine can modulate host glucose homeostasis through the regulation of metabolic hormone bioavailability ([ 9 ][10]). Sullivan et al. describe a mechanism by which γδ T lymphocytes control intestinal metabolic transcription programs. They find that in response to sugar-rich diets, γδ T lymphocytes promote CarbTP up-regulation in epithelial cells through inhibition of another population of resident intestinal immune cells, type 3 innate lymphoid cells (ILC3) (see the figure). ILC3 control intestinal host-microbiota interactions through the production of secreted factors, particularly interleukin-22 (IL-22), which instructs epithelial cells to increase barrier defense functions. IL-22 production by ILC3 is regulated by signals derived from multiple gut-resident cell types, including enteric glia ([ 10 ][11]), gut neurons ([ 4 ][4]), and other immune cells, such as macrophages ([ 11 ][12]). An inability to down-regulate IL-22 production by ILC3 results in reduced transcriptional programs associated with lipid metabolism in the intestine, as well as altered concentrations of circulating triglycerides and fatty acids ([ 2 ][2], [ 4 ][4]). Therefore, in mice, ILC3 inhibit metabolic programs associated with lipid absorption while promoting innate immune responses. Sullivan et al. describe a previously unknown role for ILC3 in intestinal metabolism, showing that γδ T lymphocytes can inhibit their production of IL-22. This inhibition is an essential step in intestinal epithelial cell adaptation to sugar-rich diets and up-regulation of CarbTP. It is still unclear how γδ T lymphocytes communicate with ILC3 to instruct down-regulation of cytokine production. Understanding this may help to identify strategies to rectify defects in nutrient absorption through the modulation of innate immune pathways. Moreover, it could also clarify whether immune-mediated alterations in intestinal absorptive functions can explain the association between an altered gut microbiota and malabsorptive dysfunctions in infants ([ 12 ][13]). Trade-off circuits that coordinate nutrition and immune defense have been described in other organisms. In some plants, a transcription factor that up-regulates responses for increasing nutrient uptake also represses immune defense genes ([ 13 ][14]). It was suggested that negative regulation of plant immune systems is relevant for the assembly of a root-associated microbiota that augments organism growth ([ 13 ][14]). If the same concept can be translated to animals, it will be important to determine whether down-regulation of ILC3-mediated immune responses by γδ T lymphocytes influences the commensal microbiota composition. Such adapted microbiota could have a major role in helping the host handle luminal increases in carbohydrates or could protect the host against intestinal colonization by some enteropathogens through niche-competition ([ 14 ][15]). Conversely, a newly assembled microbiota could also have deleterious effects, such as participating in the progression of host metabolic dysfunctions. Moreover, pathogens can exploit systems that coordinate nutritional and immune responses ([ 4 ][4], [ 15 ][16]). Therefore, it will be important to determine whether enteropathogens can modulate γδ T lymphocytes, which could lead to inhibition of ILC3-mediated host resistance to some infections. It is still unknown whether γδ T lymphocytes directly sense luminal signals (increase in sugar content) or if another cellular relay participates in transducing dietary information to γδ T lymphocytes. Sullivan et al. provide some evidence suggesting that tuft cells, specialized intestinal epithelial cells, might play a role in the up-regulation of CarbTP on a sugar-rich diet, but more studies are needed to dissect the mechanisms of interaction between epithelial cells, γδ T lymphocytes, and ILC3 in the control of metabolism. It will also be important to learn whether the on-demand regulation of CarbTP by γδ T lymphocytes contributes to overall sugar digestion and absorption. The identification of γδ T lymphocytes as decoders of nutritional input adds to our understanding of how organisms adapt to changes in nutrient availability. 1. [↵][17]1. D. Hadjieconomou et al ., Nature 587, 455 (2020). [OpenUrl][18][CrossRef][19] 2. [↵][20]1. K. Mao et al ., Nature 554, 255 (2018). [OpenUrl][21][CrossRef][22][PubMed][23] 3. [↵][24]1. Z. A. Sullivan et al ., Science 371, aba8310 (2021). [OpenUrl][25] 4. [↵][26]1. J. Talbot et al ., Nature 579, 575 (2020). [OpenUrl][27][CrossRef][28][PubMed][29] 5. [↵][30]1. T. Goda , Br. J. Nutr. 84 (Suppl 2), S245 (2000). [OpenUrl][31][CrossRef][32][PubMed][33] 6. [↵][34]1. A. C. Hayday , J. Immunol. 203, 311 (2019). [OpenUrl][35][Abstract/FREE Full Text][36] 7. [↵][37]1. K. Alves de Lima et al ., Nat. Immunol. 21, 1421 (2020). [OpenUrl][38] 8. [↵][39]1. A. C. Kohlgruber et al ., Nat. Immunol. 19, 464 (2018). [OpenUrl][40][CrossRef][41][PubMed][42] 9. [↵][43]1. S. He et al ., Nature 566, 115 (2019). [OpenUrl][44][CrossRef][45][PubMed][46] 10. [↵][47]1. S. Ibiza et al ., Nature 535, 440 (2016). [OpenUrl][48][CrossRef][49][PubMed][50] 11. [↵][51]1. A. K. Savage, 2. H.-E. Liang, 3. R. M. Locksley , J. Immunol. 199, 1912 (2017). [OpenUrl][52][Abstract/FREE Full Text][53] 12. [↵][54]1. R. Y. Chen et al ., N. Engl. J. Med. 383, 321 (2020). [OpenUrl][55] 13. [↵][56]1. G. Castrillo et al ., Nature 543, 513 (2017). [OpenUrl][57][CrossRef][58][PubMed][59] 14. [↵][60]1. J. Behnsen et al ., Immunity 40, 262 (2014). [OpenUrl][61][CrossRef][62][PubMed][63][Web of Science][64] 15. [↵][65]1. Y. T. Lu et al ., Plant Physiol. 164, 1456 (2014). [OpenUrl][66][Abstract/FREE Full Text][67] [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4 [5]: #ref-5 [6]: pending:yes [7]: #ref-6 [8]: #ref-7 [9]: #ref-8 [10]: #ref-9 [11]: #ref-10 [12]: #ref-11 [13]: #ref-12 [14]: #ref-13 [15]: #ref-14 [16]: #ref-15 [17]: #xref-ref-1-1 "View reference 1 in text" [18]: {openurl}?query=rft.jtitle%253DNature%26rft.volume%253D587%26rft.spage%253D455%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fs41586-020-2866-8%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [19]: /lookup/external-ref?access_num=10.1038/s41586-020-2866-8&link_type=DOI [20]: #xref-ref-2-1 "View reference 2 in text" [21]: {openurl}?query=rft.jtitle%253DNature%26rft.volume%253D554%26rft.spage%253D255%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fnature25437%26rft_id%253Dinfo%253Apmid%252F29364878%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [22]: /lookup/external-ref?access_num=10.1038/nature25437&link_type=DOI [23]: /lookup/external-ref?access_num=29364878&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [24]: #xref-ref-3-1 "View reference 3 in text" [25]: {openurl}?query=rft.jtitle%253DScience%26rft.volume%253D371%26rft.spage%253Daba8310%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [26]: #xref-ref-4-1 "View reference 4 in text" [27]: {openurl}?query=rft.jtitle%253DNature%26rft.volume%253D579%26rft.spage%253D575%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fs41586-020-2039-9%26rft_id%253Dinfo%253Apmid%252F32050257%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [28]: /lookup/external-ref?access_num=10.1038/s41586-020-2039-9&link_type=DOI [29]: /lookup/external-ref?access_num=32050257&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [30]: #xref-ref-5-1 "View reference 5 in text" [31]: {openurl}?query=rft.jtitle%253DBr.%2BJ.%2BNutr.%26rft.volume%253D84%26rft.spage%253DS245%26rft_id%253Dinfo%253Adoi%252F10.1079%252F096582197388626%26rft_id%253Dinfo%253Apmid%252F11242478%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [32]: /lookup/external-ref?access_num=10.1079/096582197388626&link_type=DOI [33]: /lookup/external-ref?access_num=11242478&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [34]: #xref-ref-6-1 "View reference 6 in text" [35]: {openurl}?query=rft.jtitle%253DThe%2BJournal%2Bof%2BImmunology%26rft.stitle%253DJ.%2BImmunol.%26rft.aulast%253DHayday%26rft.auinit1%253DA.%2BC.%26rft.volume%253D203%26rft.issue%253D2%26rft.spage%253D311%26rft.epage%253D320%26rft.atitle%253D%257Bgamma%257D%257Bdelta%257D%2BT%2BCell%2BUpdate%253A%2BAdaptate%2BOrchestrators%2Bof%2BImmune%2BSurveillance%26rft_id%253Dinfo%253Adoi%252F10.4049%252Fjimmunol.1800934%26rft_id%253Dinfo%253Apmid%252F31285310%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [36]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiamltbXVub2wiO3M6NToicmVzaWQiO3M6OToiMjAzLzIvMzExIjtzOjQ6ImF0b20iO3M6MjM6Ii9zY2kvMzcxLzY1MzUvMTIwMi5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30= [37]: #xref-ref-7-1 "View reference 7 in text" [38]: {openurl}?query=rft.jtitle%253DNat.%2BImmunol.%26rft.volume%253D21%26rft.spage%253D1421%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [39]: #xref-ref-8-1 "View reference 8 in text" [40]: {openurl}?query=rft.jtitle%253DNat.%2BImmunol.%26rft.volume%253D19%26rft.spage%253D464%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fs41590-018-0094-2%26rft_id%253Dinfo%253Apmid%252F29670241%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [41]: /lookup/external-ref?access_num=10.1038/s41590-018-0094-2&link_type=DOI [42]: /lookup/external-ref?access_num=29670241&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [43]: #xref-ref-9-1 "View reference 9 in text" [44]: {openurl}?query=rft.jtitle%253DNature%26rft.volume%253D566%26rft.spage%253D115%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fs41586-018-0849-9%26rft_id%253Dinfo%253Apmid%252F30700910%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [45]: /lookup/external-ref?access_num=10.1038/s41586-018-0849-9&link_type=DOI [46]: /lookup/external-ref?access_num=30700910&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [47]: #xref-ref-10-1 "View reference 10 in text" [48]: {openurl}?query=rft.jtitle%253DNature%26rft.volume%253D535%26rft.spage%253D440%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fnature18644%26rft_id%253Dinfo%253Apmid%252F27409807%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [49]: /lookup/external-ref?access_num=10.1038/nature18644&link_type=DOI [50]: /lookup/external-ref?access_num=27409807&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [51]: #xref-ref-11-1 "View reference 11 in text" [52]: {openurl}?query=rft.jtitle%253DJ.%2BImmunol.%26rft_id%253Dinfo%253Adoi%252F10.4049%252Fjimmunol.1700155%26rft_id%253Dinfo%253Apmid%252F28747343%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [53]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiamltbXVub2wiO3M6NToicmVzaWQiO3M6MTA6IjE5OS81LzE5MTIiO3M6NDoiYXRvbSI7czoyMzoiL3NjaS8zNzEvNjUzNS8xMjAyLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ== [54]: #xref-ref-12-1 "View reference 12 in text" [55]: {openurl}?query=rft.jtitle%253DN.%2BEngl.%2BJ.%2BMed.%26rft.volume%253D383%26rft.spage%253D321%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [56]: #xref-ref-13-1 "View reference 13 in text" [57]: {openurl}?query=rft.jtitle%253DNature%26rft.volume%253D543%26rft.spage%253D513%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fnature21417%26rft_id%253Dinfo%253Apmid%252F28297714%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [58]: /lookup/external-ref?access_num=10.1038/nature21417&link_type=DOI [59]: /lookup/external-ref?access_num=28297714&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [60]: #xref-ref-14-1 "View reference 14 in text" [61]: {openurl}?query=rft.jtitle%253DImmunity%26rft.volume%253D40%26rft.spage%253D262%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.immuni.2014.01.003%26rft_id%253Dinfo%253Apmid%252F24508234%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [62]: /lookup/external-ref?access_num=10.1016/j.immuni.2014.01.003&link_type=DOI [63]: /lookup/external-ref?access_num=24508234&link_type=MED&atom=%2Fsci%2F371%2F6535%2F1202.atom [64]: /lookup/external-ref?access_num=000331637600013&link_type=ISI [65]: #xref-ref-15-1 "View reference 15 in text" [66]: {openurl}?query=rft.jtitle%253DPlant%2BPhysiol.%26rft_id%253Dinfo%253Adoi%252F10.1104%252Fpp.113.229740%26rft_id%253Dinfo%253Apmid%252F24464367%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [67]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTI6InBsYW50cGh5c2lvbCI7czo1OiJyZXNpZCI7czoxMDoiMTY0LzMvMTQ1NiI7czo0OiJhdG9tIjtzOjIzOiIvc2NpLzM3MS82NTM1LzEyMDIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/319922
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jhimmy Talbot,Dan R. Littman. Immune cell control of nutrient absorption[J]. Science,2021.
APA	Jhimmy Talbot,&Dan R. Littman.(2021).Immune cell control of nutrient absorption.Science.
MLA	Jhimmy Talbot,et al."Immune cell control of nutrient absorption".Science (2021).