Group 3 ILCs (ILC3)

Key features:
Group 3 ILCs (ILC3) are remarkably similar to CD4+ Th17 cell

Stimuli:
Interleukin-1 (IL-1) beta (IL-1F2), Interleukin-23 (IL-23), TNF-like ligand 1 A (TL1A) / Vascular endothelial growth inhibitor, Short-Chain Fatty Acids (SCFAs), AHR Ligands

Effector molecules:
Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin-2 (IL-2), Interleukin-17 Family / Interleukin-17 (IL-17), Interleukin-22 (IL-22)

Major effects:
Maintenance of Group 3 ILCs (ILC3), Group 3 ILCs (ILC3) Expansion and proliferation, Homeostasis of Regulatory T Cells (Tregs), Regulation of CD4 responses in the gut via MHC Class II Group 3 ILCs (ILC3)

References:

Kempski et al. 2017
Song et al. 2020e

While Group 3 ILCs (ILC3) produce IL-22 , IL-17A and Interleukin-17F (IL-17F)(brain://x3_rdyK3A0qdZ0lNEY4fug/Il17f), Lymphoid Tissue Inducer Cells (LTi cells) are mainly involved in lymphoid organ formation through the production of lymphotoxins
Vivier et al. 2018
Klose & Diefenbach 2014 Curr Top Microbiol Immunol 381: 215-55 (11)
Ganal-Vonarburg & Duerr 2021 Immunology 159: 39-51

A dialogue between ILC3s and T cells via the Major Histocompatibility Complex Class II (MHC-II) is necessary to support colonization with microbiota, which then induce type 1 immunity in the gut and in the tumor microenvironment. People with dysregulated intestinal ILC3s harbor microbiota that, when transferred to mice, do not induce type 1 immunity and immunotherapy responsiveness
Goc et al. 2021 Cell 184:

Tissue-resident ILC3s promote tolerance. ILC3s from the circulation infiltrates the Central Nervous System (CNS) during neuroinflammation based on mouse experiments. ILC3s infiltrate the CNS in a mouse model of Multiple Sclerosis (MS). These ILC3s are derived from the circulation, localize in proximity to infiltrating T cells in the CNS (pro-inflammatory T cells), function as antigen-presenting cells that restimulate myelin-specific T cells, and are increased in individuals with Multiple Sclerosis (MS) (neuroinflammation). Conventional and tissue-resident ILC3s in the periphery do not appear to contribute to disease (Multiple Sclerosis) induction
Grigg et al. 2021 Nature 600: 707

IL-22 is predominantly produced by CD4+ T cells and ILC3 populations, among others
Sabihi et al. 2020 Cells 9: 2205

Group 3 ILCs are defined by their capacity to produce cytokines Interleukin-17A (IL-17A) and/or IL-22 and Interleukin-23 (IL-23). Group 3 innate lymphoid cells (ILC3s) not only play a protective role in maintaining intestinal homeostasis and gut barrier function, but also a pathogenic role in intestinal inflammation
Song et al. 2020e

Among the Innate lymphoid cells (ILCs), Group 3 ILCs (ILC3) are the most important with regard to the gut microbiota. Also, Type 3 ILCs exist mainly in mucosal tissue and at low levels in the spleen and liver. Group 3 ILCs (ILC3) can control the activation of autoreactive CD4+ T cells in the lamina propria by expressing the major histocompatibility complex II (MHC-II). They can drive immune tolerance in the host gut by controlling the function of other immune cells.
Wu & Shen 2020 Front. Immunol. 11: 554880

The Group 3 ILCs (ILC3) produce neurotrophic factor signals after interacting with enteric glial cells
Ibiza et al. 2016 Nature 535(7612): 440-443
Han et al. 2019a Mediators Inflammation 2019: 1978094

ILC3s have emerged as a critical subset in the gut. They are the most phenotypically diverse ILC population and interact directly with numerous different cell types (haematopoietic and non-haematopoeitic), as well as interface with the bacterial flora
Pantazi & Powell 2019

Group 3 ILCs (ILC3) are dependent on the RAR-related orphan receptor gamma/t (ROR-gamma/t) Isoform 2 (NR1F3) and the aryl hydrocarbon receptor (AHR) and release Interleukin-17 Family / Interleukin-17 (IL-17) and IL-22
Spits et al. 2013 Nat. Rev. Immunol. 13: 145-149
Montaldo et al. 2015 Eur J Immunol. 45(8): 2171-82
Kempski et al. 2017
Colonna 2018 Immunity 48: 1104-1117
Li & Glover 2018 Arch Immunol Ther Exp (Warsz) 66(6): 415-21

Type 3 ILCs express Interleukin-1 (IL-1) receptors (IL-1R) and Interleukin-23 Receptor (IL23R)
Li & Glover 2018 Arch Immunol Ther Exp (Warsz) 66(6): 415-21

Group 3 ILCs (ILC3) reinforce the epithelial barrier and maintain homeostasis with gut microbiota
Chea et al. 2016 Sci Signal. 9(426): ra45

It has been found that MHC II-expressing CCR6 + type 3 ILCs control intestinal homeostasis by inducing apoptotic cell death and deleting the activation of commensal bacterial-specific T cells
Hepworth et al. 2013 Nature 498(7452): 113-7
Hepworth et al. 2015 Science 348(6238): 1031-5

Candidatus Savagella (Segmented filamentous bacteria/SFB) colonization in mice activates innate lymphoid cells (ILC3) to secrete Interleukin-22 (IL-22) that induces serum amyloid A protein 1 and 2, production to promote local Interleukin-17A (IL-17A) responses
Sano et al. 2015 Cell 163: 381–393

MHC II + type 3 ILC could represent a new therapeutic target to control pathological CD4+ T cell responses in chronic inflammatory diseases
Hooper et al. 2012
Belkaid & Hand 2014 Cell 157: 121-141

Hepworth et al. (2013) showed that ILC3s could process as well as present antigen to T-cells.
Hepworth et al. 2013 Nature 498(7452): 113-7

RAR-related orphan receptor gamma/t (ROR-gamma/t) Isoform 2 (NR1F3) ILCs (ROR-gamma/t + ILC) are the major source of intestinal Interleukin-22 (IL-22) that is dependent on Aryl Hydrocarbon Receptor (AhR)
Qiu et al. 2012 Immunity. 36: 92-104

Group 3 ILCs (ILC3) express the Th17 / Th22 cell master regulator RAR-related orphan receptor gamma/t (ROR-gamma/t) (NR1F3) and their effector cytokines Interleukin-22 / IL-22 Receptor (IL-22R), Interleukin-17A (IL-17A), and Interleukin-17F (IL-17F)
Satoh-Takayama et al. 2008 Immunity 29: 958
Buonocore et al. 2010 Nature 464: 1371
Sonnenberg et al. 2011 Immunity 34:122–134.

see also:
Group 3 ILCs (ILC3) & Gut microbiota
Group 3 ILCs (ILC3) & RAR-related orphan receptor gamma/t (ROR-gamma/t) (NR1F3)