TY - JOUR
T1 - Proline uptake promotes activation of lymphoid tissue inducer cells to maintain gut homeostasis
AU - Wu, Di
AU - Li, Zongxian
AU - Zhang, Yime
AU - Zhang, Yinlian
AU - Ren, Guanqun
AU - Zeng, Yanyu
AU - Liu, Huiying
AU - Guan, Weiqiang
AU - Zhao, Xingyu
AU - Li, Peng
AU - Hu, Luni
AU - Hou, Zhiyuan
AU - Gong, Jingjing
AU - Li, Jun
AU - Jin, Wenfei
AU - Hu, Zeping
AU - Jiang, Changtao
AU - Li, Houhua
AU - Zhong, Chao
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/11
Y1 - 2023/11
N2 - Metabolic regulation is integral to the proper functioning of innate lymphoid cells, yet the underlying mechanisms remain elusive. Here, we show that disruption of exogenous proline uptake, either through dietary restriction or by deficiency of the proline transporter Slc6a7, in lymphoid tissue inducer (LTi) cells, impairs LTi activation and aggravates dextran sodium sulfate-induced colitis in mice. With an integrative transcriptomic and metabolomic analysis, we profile the metabolic characteristics of various innate lymphoid cell subsets and reveal a notable enrichment of proline metabolism in LTi cells. Mechanistically, defective proline uptake diminishes the generation of reactive oxygen species, previously known to facilitate LTi activation. Additionally, LTi cells deficient in Slc6a7 display downregulation of Cebpb and Kdm6b, resulting in compromised transcriptional and epigenetic regulation of interleukin-22. Furthermore, our study uncovers the therapeutic potential of proline supplementation in alleviating colitis. Therefore, these findings shed light on the role of proline in facilitating LTi activation and ultimately contributing to gut homeostasis.
AB - Metabolic regulation is integral to the proper functioning of innate lymphoid cells, yet the underlying mechanisms remain elusive. Here, we show that disruption of exogenous proline uptake, either through dietary restriction or by deficiency of the proline transporter Slc6a7, in lymphoid tissue inducer (LTi) cells, impairs LTi activation and aggravates dextran sodium sulfate-induced colitis in mice. With an integrative transcriptomic and metabolomic analysis, we profile the metabolic characteristics of various innate lymphoid cell subsets and reveal a notable enrichment of proline metabolism in LTi cells. Mechanistically, defective proline uptake diminishes the generation of reactive oxygen species, previously known to facilitate LTi activation. Additionally, LTi cells deficient in Slc6a7 display downregulation of Cebpb and Kdm6b, resulting in compromised transcriptional and epigenetic regulation of interleukin-22. Furthermore, our study uncovers the therapeutic potential of proline supplementation in alleviating colitis. Therefore, these findings shed light on the role of proline in facilitating LTi activation and ultimately contributing to gut homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=85174287307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85174287307&partnerID=8YFLogxK
U2 - 10.1038/s42255-023-00908-6
DO - 10.1038/s42255-023-00908-6
M3 - Article
C2 - 37857730
AN - SCOPUS:85174287307
SN - 2522-5812
VL - 5
SP - 1953
EP - 1968
JO - Nature Metabolism
JF - Nature Metabolism
IS - 11
ER -