A17 THE NEUROPEPTIDE VIP REGULATES INTESTINAL IMMUNITY THROUGH MODULATING THE ACTIVATION AND RECRUITMENT OF GROUP 3 INNATE LYMPHOID CELLS

CCR6− group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features and fully convert into ILC1s. The molecular mechanisms governing such plasticity are undefined. Here, we identified c-Maf as an essential regulator of ILC3 homeostasis and plasticity that limits physiological ILC1 conversion. Phenotypic analysis of effector status in Maf-deficient CCR6− ILC3s, coupled with evaluation of global changes in transcriptome, chromatin accessibility, and transcription factor motif enrichment, revealed that c-Maf enforces ILC3 identity. c-Maf promoted ILC3 accessibility and supported RORγt activity and expression of type 3 effector genes. Conversely, c-Maf antagonized type 1 programming, largely through restraint of T-bet expression and function. Mapping of the dynamic changes in chromatin landscape accompanying CCR6− ILC3 development and ILC1 conversion solidified c-Maf as a gatekeeper of type 1 regulatory transformation and a controller of ILC3 fate.

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The Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.586471 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dan Yang ◽

Xinning Guo ◽

Tingxuan Huang ◽

Chuntao Liu

Keyword(s):

Respiratory Infections ◽

Inflammatory Diseases ◽

Pulmonary Inflammation ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Intestinal Immunity ◽

Group 3 ◽

Underlying Mechanisms ◽

And Function ◽

Pathogen Clearance

The lung is constantly exposed to environmental particulates such as aeroallergens, pollutants, or microorganisms and is protected by a poised immune response. Innate lymphoid cells (ILCs) are a population of immune cells found in a variety of tissue sites, particularly barrier surfaces such as the lung and the intestine. ILCs play a crucial role in the innate immune system, and they are involved in the maintenance of mucosal homeostasis, inflammation regulation, tissue remodeling, and pathogen clearance. In recent years, group 3 innate lymphoid cells (ILC3s) have emerged as key mediators of mucosal protection and repair during infection, mainly through IL-17 and IL-22 production. Although research on ILC3s has become focused on the intestinal immunity, the biology and function of pulmonary ILC3s in the pathogenesis of respiratory infections and in the development of chronic pulmonary inflammatory diseases remain elusive. In this review, we will mainly discuss how pulmonary ILC3s act on protection against pathogen challenge and pulmonary inflammation, as well as the underlying mechanisms.

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Faculty Opinions recommendation of Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733518679.793551473 ◽

2018 ◽

Author(s):

Andrea Reboldi

Keyword(s):

G Protein ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Lymphoid Tissues ◽

G Protein Coupled Receptor ◽

Group 3 ◽

G Protein Coupled

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Gata3 drives development of RORγt+ group 3 innate lymphoid cells

Journal of Experimental Medicine ◽

10.1084/jem.20131038 ◽

2014 ◽

Vol 211 (2) ◽

pp. 199-208 ◽

Cited By ~ 152

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.

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