Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes.
NOD2 functions as an intracellular sensor for microbial pathogen and plays an important role in epithelial defense. The loss-of-function mutation of NOD2 is strongly associated with human Crohn's disease (CD). However, the mechanisms of how NOD2 maintains the intestinal homeostasis and regulates the susceptibility of CD are still unclear. Here we found that the numbers of intestinal intraepithelial lymphocytes (IELs) were reduced significantly in Nod2(-/-) mice and the residual IELs displayed reduced proliferation and increased apoptosis. Further study showed that NOD2 signaling maintained IELs via recognition of gut microbiota and IL-15 production. Notably, recovery of IELs by adoptive transfer could reduce the susceptibility of Nod2(-/-) mice to the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Our results demonstrate that recognition of gut microbiota by NOD2 is important to maintain the homeostasis of IELs and provide a clue that may link NOD2 variation to the impaired innate immunity and higher susceptibility in CD.
the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
Wei
W
Jiang
Xiaqiong
X
Wang
Benhua
B
Zeng
Lei
L
Liu
Aubry
A
Tardivel
Hong
H
Wei
Jiahuai
J
Han
H Robson
HR
MacDonald
Jurg
J
Tschopp
Zhigang
Z
Tian
Rongbin
R
Zhou
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D019587:Dietary Supplements; D004198:Disease Susceptibility; D004848:Epithelium / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006413:Hematopoietic System / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000378:metabolism*; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D014302:Trinitrobenzenesulfonic Acid
D019409:Interleukin-15; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D014302:Trinitrobenzenesulfonic Acid; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse