scholarly journals Distinct requirements for T-bet in gut innate lymphoid cells

2012 ◽  
Vol 209 (13) ◽  
pp. 2331-2338 ◽  
Author(s):  
Giuseppe Sciumé ◽  
Kiyoshi Hirahara ◽  
Hayato Takahashi ◽  
Arian Laurence ◽  
Alejandro V. Villarino ◽  
...  
Keyword(s):  
Marked Reduction ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Heterogeneous Population ◽  
Lymphoid Cells ◽  
Natural Cytotoxicity ◽  
Bone Marrow Chimera ◽  
Intestinal Lamina Propria ◽  
General Importance ◽  
A Cell

Interleukin (IL)-22–producing innate lymphoid cells (ILCs; ILC22) comprise a heterogeneous population of cells that are dependent on the transcription factor retinoid-related orphan γt (RORγt) and are critical for barrier function of the intestinal mucosa. A distinct ILC22 subset expresses the natural cytotoxicity receptor NKp46 (NKp46+ ILC22); however, the factors that contribute to the generation of this population versus other subsets are largely unknown. Herein, we show that T-bet (encoded by Tbx21) was highly expressed in NKp46+ ILC22, a feature shared by all NKp46+ cells present in the intestine but not by other IL-22–producing populations. Accordingly, the absence of T-bet resulted in loss of NKp46+ ILC22 in the intestinal lamina propria. The residual NKp46+ ILC22 present in Tbx21−/− mice showed a marked reduction of Rorγt expression and impairment in IL-22 production. Generation and functions of gut NK1.1+ cells were also altered. Bone marrow chimera experiments revealed a cell-intrinsic requirement for T-bet in these subsets and competitive reconstitution experiments revealed roles for T-bet in multiple ILC subsets. Thus, T-bet has a general importance for ILC in the gut and plays a selective and critical role in the generation of NKp46+ ILC22.

scholarly journals T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo

2020 ◽  
Author(s):  
J-H Schroeder ◽  
N Garrido-Mesa ◽  
T Zabinski ◽  
AL Gallagher ◽  
L Campbell ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Fate Mapping ◽  
Functional Roles ◽  
Mucosal Surfaces ◽  
Group 2

ABSTRACTInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are “fate-mapped” for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces.SUMMARYInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Three distinct ILC groups have been described according to expression of subset defining transcription factors and other markers. In this study we characterize a novel ILC subset with characteristics of group 1 and group 2 ILC in vivo.

scholarly journals Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells

2019 ◽  
Vol 20 (11) ◽  
pp. 2836 ◽  
Author(s):  
Grace Mallett ◽  
Arian Laurence ◽  
Shoba Amarnath
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Cell Surface Receptor ◽  
Programmed Cell Death 1 ◽  
Surface Receptor ◽  
A Cell ◽  
And Function

Programmed cell death-1 (PD-1) is a cell surface receptor that dampens adaptive immune responses. PD-1 is activated by the engagement of its ligands PDL-1 or PDL-2. This results in the inhibition of T cell proliferation, differentiation, cytokine secretion, and cytolytic function. Although a great deal is known about PD-1 mediated regulation of CD4+ and CD8+ T cells, its expression and function in innate lymphoid cells (ILCs) are yet to be fully deciphered. This review summarizes the role of PD-1 in (1) modulating ILC development, (2) ILC function, and (3) PD-1 signaling in ILC. Finally, we explore how PD-1 based immunotherapies may be beneficial in boosting ILC responses in cancer, infections, and other immune-related disorders.

scholarly journals Innate Lymphoid Cells in Skin Homeostasis and Malignancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Marek Wagner ◽  
Shigeo Koyasu
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Antigen Receptors ◽  
First Line ◽  
Adaptive Immune ◽  
Skin Malignancy ◽  
Barrier Tissues

Innate lymphoid cells (ILCs) are mostly tissue resident lymphocytes that are preferentially enriched in barrier tissues such as the skin. Although they lack the expression of somatically rearranged antigen receptors present on T and B cells, ILCs partake in multiple immune pathways by regulating tissue inflammation and potentiating adaptive immunity. Emerging evidence indicates that ILCs play a critical role in the control of melanoma, a type of skin malignancy thought to trigger immunity mediated mainly by adaptive immune responses. Here, we compile our current understanding of ILCs with regard to their role as the first line of defence against melanoma development and progression. We also discuss areas that merit further investigation. We envisage that the possibility to harness therapeutic potential of ILCs might benefit patients suffering from skin malignancies such as melanoma.

Innate Lymphoid Cells are Dysregulated after Intestinal Transplantation and Play a Critical Role in Regulating Allograft Homeostasis

2017 ◽  
Vol 101 ◽  
pp. S63
Author(s):  
Priscilla Cha ◽  
Brenna Houlihan ◽  
Oswaldo Aguirre ◽  
Jason Kaiser ◽  
Brian Monahan ◽  
...  
Keyword(s):  
Critical Role ◽  
Intestinal Transplantation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

scholarly journals Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection

2016 ◽  
Vol 213 (8) ◽  
pp. 1409-1418 ◽  
Author(s):  
Christoph Wilhelm ◽  
Oliver J. Harrison ◽  
Vanessa Schmitt ◽  
Martin Pelletier ◽  
Sean P. Spencer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Helminth Infection ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Environmental Signals ◽  
Essential Nutrient ◽  
Barrier Immunity

Innate lymphoid cells (ILC) play an important role in many immune processes, including control of infections, inflammation, and tissue repair. To date, little is known about the metabolism of ILC and whether these cells can metabolically adapt in response to environmental signals. Here we show that type 2 innate lymphoid cells (ILC2), important mediators of barrier immunity, predominantly depend on fatty acid (FA) metabolism during helminth infection. Further, in situations where an essential nutrient, such as vitamin A, is limited, ILC2 sustain their function and selectively maintain interleukin 13 (IL-13) production via increased acquisition and utilization of FA. Together, these results reveal that ILC2 preferentially use FAs to maintain their function in the context of helminth infection or malnutrition and propose that enhanced FA usage and FA-dependent IL-13 production by ILC2 could represent a host adaptation to maintain barrier immunity under dietary restriction.

scholarly journals IL-33 promotes the egress of group 2 innate lymphoid cells from the bone marrow

2017 ◽  
Vol 215 (1) ◽  
pp. 263-281 ◽  
Author(s):  
Matthew T. Stier ◽  
Jian Zhang ◽  
Kasia Goleniewska ◽  
Jacqueline Y. Cephus ◽  
Mark Rusznak ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Critical Role ◽  
Allergic Inflammation ◽  
Allergen Challenge ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Effector Cells ◽  
Group 2 ◽  
Fungal Allergen ◽  
Key Participants

Group 2 innate lymphoid cells (ILC2s) are effector cells within the mucosa and key participants in type 2 immune responses in the context of allergic inflammation and infection. ILC2s develop in the bone marrow from common lymphoid progenitor cells, but little is known about how ILC2s egress from the bone marrow for hematogenous trafficking. In this study, we identified a critical role for IL-33, a hallmark peripheral ILC2-activating cytokine, in promoting the egress of ILC2 lineage cells from the bone marrow. Mice lacking IL-33 signaling had normal development of ILC2s but retained significantly more ILC2 progenitors in the bone marrow via augmented expression of CXCR4. Intravenous injection of IL-33 or pulmonary fungal allergen challenge mobilized ILC2 progenitors to exit the bone marrow. Finally, IL-33 enhanced ILC2 trafficking to the lungs in a parabiosis mouse model of tissue disruption and repopulation. Collectively, these data demonstrate that IL-33 plays a critical role in promoting ILC2 egress from the bone marrow.

scholarly journals Brg1 restrains the pro-inflammatory properties of ILC3s and modulates intestinal immunity

2020 ◽  
Vol 14 (1) ◽  
pp. 38-52
Author(s):  
Xinyi Qi ◽  
Jinxin Qiu ◽  
Jiali Chang ◽  
Yan Ji ◽  
Qi Yang ◽  
...  
Keyword(s):  
Gene Locus ◽  
Intestinal Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Intestinal Immunity ◽  
Baf Complex ◽  
Gm Csf ◽  
A Cell ◽  
And Function ◽  
Csf Production

AbstractGroup 3 innate lymphoid cells (ILC3s), a subset of the innate lymphoid cells, are abundantly present in the intestine and are crucial regulators of intestinal inflammation. Brg1 (Brahma-related gene 1), a catalytic subunit of the mammalian SWI-SNF-like chromatin-remodeling BAF complex, regulates the development and function of various immune cells. Here, by genetic deletion of Brg1 in ILC3s (Smarca4ΔILC3), we prove that Brg1 supports the differentiation of NKp46+ILC3s by promoting the T-bet expression in NKp46−ILC3s, which facilitates the conversion of NKp46−ILC3s to NKp46+ILC3s. Strikingly, Smarca4ΔILC3 mice of the Rag1−/− background develop spontaneous colitis accompanied with increased GM-CSF production in ILC3s. By construction of a mixed bone marrow chimeric system, we demonstrate that Brg1 enhances T-bet and inhibits GM-CSF expression in ILC3s through a cell-intrinsic manner. Blockade of GM-CSF ameliorates colitis in Rag1−/−Smarca4ΔILC3 mice, suggesting that the suppression of GM-CSF production from ILC3s by Brg1 serves as a critical mechanism for Brg1 to restrain intestinal inflammation. We have further demonstrated that Brg1 binds to the Tbx21 and Csf2 gene locus in ILC3s, and favors the active and repressive histones modifications on gene locus of Tbx21 and Csf2 respectively. Our work reveals the essential role of Brg1 in intestinal immunity by regulating ILC3s.

scholarly journals Interleukin-12 and -23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

Immunity ◽  
2015 ◽  
Vol 43 (1) ◽  
pp. 146-160 ◽  
Author(s):  
Jochem H. Bernink ◽  
Lisette Krabbendam ◽  
Kristine Germar ◽  
Esther de Jong ◽  
Konrad Gronke ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Interleukin 12 ◽  
Intestinal Lamina Propria ◽  
Group 3 ◽  
Group 1

scholarly journals Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens

2014 ◽  
Vol 211 (9) ◽  
pp. 1723-1731 ◽  
Author(s):  
Theresa L. Geiger ◽  
Michael C. Abt ◽  
Georg Gasteiger ◽  
Matthew A. Firth ◽  
Margaret H. O’Connor ◽  
...  
Keyword(s):  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Immune Defense ◽  
Lymphoid Cells ◽  
Bzip Transcription Factor ◽  
Host Protection ◽  
Intestinal Pathogens ◽  
And Function ◽  
Type 3 ◽  
Deficient Mice

The bZIP transcription factor Nfil3 (also known as E4BP4) is required for the development of natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s). We find that Nfil3 plays a critical role in the development of other mucosal tissue-associated innate lymphocytes. Type 3 ILCs (ILC3s), including lymphoid tissue inducer (LTi)–like cells, are severely diminished in both numbers and function in Nfil3-deficient mice. Using mixed bone marrow chimeric mice, we demonstrate that Nfil3 is critical for normal development of gut-associated ILC3s in a cell-intrinsic manner. Furthermore, Nfil3 deficiency severely compromises intestinal innate immune defense against acute bacterial infection with Citrobacter rodentium and Clostridium difficile. Nfil3 deficiency resulted in a loss of the recently identified ILC precursor, yet conditional ablation of Nfil3 in the NKp46+ ILC3 subset did not perturb ILC3 numbers, suggesting that Nfil3 is required early during ILC3 development but not for lineage maintenance. Lastly, a marked defect in type 2 ILCs (ILC2s) was also observed in the lungs and visceral adipose tissue of Nfil3-deficient mice, revealing a general requirement for Nfil3 in the development of all ILC lineages.

scholarly journals Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 559
Author(s):  
Qiutong Huang ◽  
Nicolas Jacquelot ◽  
Adele Preaudet ◽  
Soroor Hediyeh-zadeh ◽  
Fernando Souza-Fonseca-Guimaraes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
Gene Signature ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Clinical Prognosis ◽  
Tumour Immunity ◽  
Colorectal Cancer Progression

Chronic inflammation of the gastrointestinal (GI) tract contributes to colorectal cancer (CRC) progression. While the role of adaptive T cells in CRC is now well established, the role of innate immune cells, specifically innate lymphoid cells (ILCs), is not well understood. To define the role of ILCs in CRC we employed complementary heterotopic and chemically-induced CRC mouse models. We discovered that ILCs were abundant in CRC tumours and contributed to anti-tumour immunity. We focused on ILC2 and showed that ILC2-deficient mice developed a higher tumour burden compared with littermate wild-type controls. We generated an ILC2 gene signature and using machine learning models revealed that CRC patients with a high intratumor ILC2 gene signature had a favourable clinical prognosis. Collectively, our results highlight a critical role for ILC2 in CRC, suggesting a potential new avenue to improve clinical outcomes through ILC2-agonist based therapeutic approaches.

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