Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells

2021 ◽  
Vol 118 (41) ◽  
pp. e2106634118
Author(s):  
Hong Bing Yu ◽  
Hyungjun Yang ◽  
Joannie M. Allaire ◽  
Caixia Ma ◽  
Franziska A. Graef ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Host Defense ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Enteric Pathogens ◽  
Lymphoid Tissues ◽  
Homing Receptor ◽  
Local Populations ◽  
Ccr9 Expression ◽  
Group 3

Group 3 innate lymphoid cells (ILC3s) control the formation of intestinal lymphoid tissues and play key roles in intestinal defense. They express neuropeptide vasoactive intestinal peptide (VIP) receptor 2 (VPAC2), through which VIP modulates their function, but whether VIP exerts other effects on ILC3 remains unclear. We show that VIP promotes ILC3 recruitment to the intestine through VPAC1 independent of the microbiota or adaptive immunity. VIP is also required for postnatal formation of lymphoid tissues as well as the maintenance of local populations of retinoic acid (RA)–producing dendritic cells, with RA up-regulating gut-homing receptor CCR9 expression by ILC3s. Correspondingly, mice deficient in VIP or VPAC1 suffer a paucity of intestinal ILC3s along with impaired production of the cytokine IL-22, rendering them highly susceptible to the enteric pathogen Citrobacter rodentium. This heightened susceptibility to C. rodentium infection was ameliorated by RA supplementation, adoptive transfer of ILC3s, or by recombinant IL-22. Thus, VIP regulates the recruitment of intestinal ILC3s and formation of postnatal intestinal lymphoid tissues, offering protection against enteric pathogens.

scholarly journals Group 3 innate lymphoid cells mediate host defense against attaching and effacing pathogens

2021 ◽  
Vol 63 ◽  
pp. 83-91
Author(s):  
Angélique Jarade ◽  
James P Di Santo ◽  
Nicolas Serafini
Keyword(s):  
Host Defense ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 3

scholarly journals Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues

Immunity ◽  
2020 ◽  
Vol 53 (5) ◽  
pp. 1015-1032.e8
Author(s):  
Fabian Guendel ◽  
Michael Kofoed-Branzk ◽  
Konrad Gronke ◽  
Caroline Tizian ◽  
Mario Witkowski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Distinct Subset ◽  
Group 3

scholarly journals Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183

Cell Reports ◽  
2018 ◽  
Vol 23 (13) ◽  
pp. 3750-3758 ◽  
Author(s):  
Coco Chu ◽  
Saya Moriyama ◽  
Zhi Li ◽  
Lei Zhou ◽  
Anne-Laure Flamar ◽  
...  
Keyword(s):  
G Protein ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
G Protein Coupled Receptor ◽  
Group 3 ◽  
G Protein Coupled

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 Delineating spatiotemporal and hierarchical development of human fetal innate lymphoid cells

Cell Research ◽  
2021 ◽  
Author(s):  
Chen Liu ◽  
Yandong Gong ◽  
Han Zhang ◽  
Hua Yang ◽  
Yang Zeng ◽  
...  
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Fetal Liver ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Hematopoietic Stem ◽  
Molecular Features ◽  
Lymphoid Progenitors ◽  
B Lineage

AbstractWhereas the critical roles of innate lymphoid cells (ILCs) in adult are increasingly appreciated, their developmental hierarchy in early human fetus remains largely elusive. In this study, we sorted human hematopoietic stem/progenitor cells, lymphoid progenitors, putative ILC progenitor/precursors and mature ILCs in the fetal hematopoietic, lymphoid and non-lymphoid tissues, from 8 to 12 post-conception weeks, for single-cell RNA-sequencing, followed by computational analysis and functional validation at bulk and single-cell levels. We delineated the early phase of ILC lineage commitment from hematopoietic stem/progenitor cells, which mainly occurred in fetal liver and intestine. We further unveiled interleukin-3 receptor as a surface marker for the lymphoid progenitors in fetal liver with T, B, ILC and myeloid potentials, while IL-3RA– lymphoid progenitors were predominantly B-lineage committed. Notably, we determined the heterogeneity and tissue distribution of each ILC subpopulation, revealing the proliferating characteristics shared by the precursors of each ILC subtype. Additionally, a novel unconventional ILC2 subpopulation (CRTH2– CCR9+ ILC2) was identified in fetal thymus. Taken together, our study illuminates the precise cellular and molecular features underlying the stepwise formation of human fetal ILC hierarchy with remarkable spatiotemporal heterogeneity.

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
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