scholarly journals A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut

2019 ◽  
Vol 4 (40) ◽  
pp. eaax1215 ◽  
Author(s):  
Fei Teng ◽  
Jeremy Goc ◽  
Lei Zhou ◽  
Coco Chu ◽  
Manish A. Shah ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Target Genes ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Expression Of Genes ◽  
Microbe Interactions ◽  
Inflammatory Bowel ◽  
Group 3 ◽  
Host Microbe Interactions ◽  
Specific Deletion

Group 3 innate lymphoid cells (ILC3s) critically orchestrate host-microbe interactions in the healthy mammalian intestine and become substantially impaired in the context of inflammatory bowel disease (IBD). However, the molecular pathways controlling the homeostasis of ILC3s remain incompletely defined. Here, we identify that intestinal ILC3s are highly enriched in expression of genes involved in the circadian clock and exhibit diurnal oscillations of these pathways in response to light cues. Classical ILC3 effector functions also exhibited diurnal oscillations, and lineage-specific deletion of BMAL1, a master regulator of the circadian clock, resulted in markedly reduced ILC3s selectively in the intestine. BMAL1-deficient ILC3s exhibit impaired expression of Nr1d1 and Per3, hyperactivation of RORγt-dependent target genes, and elevated proapoptotic pathways. Depletion of the microbiota with antibiotics partially reduced the hyperactivation of BMAL1-deficient ILC3s and restored cellular homeostasis in the intestine. Last, ILC3s isolated from the inflamed intestine of patients with IBD exhibit substantial alterations in expression of several circadian-related genes. Our results collectively define that circadian regulation is essential for the homeostasis of ILC3s in the presence of a complex intestinal microbiota and that this pathway is disrupted in the context of IBD.

scholarly journals Dichotomous regulation of group 3 innate lymphoid cells by nongastric Helicobacter species

2019 ◽  
Vol 116 (49) ◽  
pp. 24760-24769 ◽  
Author(s):  
John W. Bostick ◽  
Yetao Wang ◽  
Zeli Shen ◽  
Yong Ge ◽  
Jeffrey Brown ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Proliferative Capacity ◽  
Microbe Interactions ◽  
Group 3 ◽  
Host Microbe Interactions ◽  
Immunocompromised Mice ◽  
Opposing Effects

Intestinal innate lymphoid cells (ILCs) contribute to the protective immunity and homeostasis of the gut, and the microbiota are critically involved in shaping ILC function. However, the role of the gut microbiota in regulating ILC development and maintenance still remains elusive. Here, we identified opposing effects on ILCs by two Helicobacter species, Helicobacter apodemus and Helicobacter typhlonius, isolated from immunocompromised mice. We demonstrated that the introduction of both Helicobacter species activated ILCs and induced gut inflammation; however, these Helicobacter species negatively regulated RORγt+ group 3 ILCs (ILC3s), especially T-bet+ ILC3s, and diminished their proliferative capacity. Thus, these findings underscore a previously unknown dichotomous regulation of ILC3s by Helicobacter species, and may serve as a model for further investigations to elucidate the host–microbe interactions that critically sustain the maintenance of intestinal ILC3s.

Oral Supplementation With Selected Lactobacillus Acidophilus Triggers Antimicrobial Response, Activation of Innate Lymphoid Cells Type 3 And Improves Colitis

2021 ◽  
Author(s):  
Jiří Hrdý ◽  
Aurélie Couturier-Maillard ◽  
Denise Boutillier ◽  
Carmen Lapadatescu ◽  
Philippe Blanc ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Lactobacillus Acidophilus ◽  
Target Genes ◽  
Intestinal Inflammation ◽  
Probiotic Strain ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Trinitrobenzene Sulfonic Acid ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that are illustrated by direct and indirect antimicrobial activity against several pathogens and improvement of intestinal inflammation. In this study, we evaluated the anti-inflammatory properties of the L. acidophilus strain BIO5768 and assessed the underlying mechanisms of action. BIO5768 was able to counteract the acute colitis that is induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was also able to alleviate intestinal inflammation induced by Citrobacter rodentium infection. Supplementation of naïve mice with either strain BIO5768 alone or as mixture, increased the gene expression of several target genes involved in immune signaling, including c-type lectin Reg3 gamma. Consistently, the ability of innate lymphoid cells to secrete IL-22 was enhanced in response to BIO5768. Interestingly, the aforementioned responses were shown to be independent of NOD2 and Th17 signaling in mice that were mono-colonized with BIO5768. In conclusion, we identify a new potential probiotic strain with the ability for the management of inflammatory bowel diseases, and provide some insights into its mode of action.

scholarly journals Gata3 drives development of RORγt+ group 3 innate lymphoid cells

2014 ◽  
Vol 211 (2) ◽  
pp. 199-208 ◽  
Author(s):  
Nicolas Serafini ◽  
Roel G.J. Klein Wolterink ◽  
Naoko Satoh-Takayama ◽  
Wei Xu ◽  
Christian A.J. Vosshenrich ◽  
...  
Keyword(s):  
T Cell ◽  
Fetal Liver ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
T Cell Subsets ◽  
Mucosal Barrier ◽  
Hematopoietic Stem ◽  
Mucosal Surfaces ◽  
Gata3 Expression ◽  
Group 3

Group 3 innate lymphoid cells (ILC3) include IL-22–producing NKp46+ cells and IL-17A/IL-22–producing CD4+ lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal RORγt+ ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut RORγt+ ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets.

scholarly journals Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells

2018 ◽  
Vol 141 (1) ◽  
pp. 279-292 ◽  
Author(s):  
Viktoria Konya ◽  
Paulo Czarnewski ◽  
Marianne Forkel ◽  
Anna Rao ◽  
Efthymia Kokkinou ◽  
...  
Keyword(s):  
Vitamin D ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 3

scholarly journals Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells

Science ◽  
2015 ◽  
Vol 348 (6238) ◽  
pp. 1031-1035 ◽  
Author(s):  
M. R. Hepworth ◽  
T. C. Fung ◽  
S. H. Masur ◽  
J. R. Kelsen ◽  
F. M. McConnell ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Commensal Bacteria ◽  
Group 3 ◽  
Selection Of
Sign in / Sign up

Export Citation Format

Share Document