scholarly journals Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans

2019 ◽  
Vol 4 (36) ◽  
pp. eaav7638 ◽  
Author(s):  
Franz Puttur ◽  
Laura Denney ◽  
Lisa G. Gregory ◽  
Juho Vuononvirta ◽  
Robert Oliver ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Lymphoid Cells ◽  
Perivascular Spaces ◽  
Cell Dynamics ◽  
Mucosal Tissues ◽  
Migratory Patterns ◽  
Group 2 ◽  
Environmental Exploration ◽  
Type 2 Inflammation

Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell–derived cytokines initiating type 2 inflammation. During inflammation, ILC2 numbers are increased in the lung. However, the mechanisms controlling ILC2 trafficking and motility within inflamed lungs remain unclear and are crucial for understanding ILC2 function in pulmonary immunity. Using several approaches, including lung intravital microscopy, we demonstrate that pulmonary ILC2s are highly dynamic, exhibit amoeboid-like movement, and aggregate in the lung peribronchial and perivascular spaces. They express distinct chemokine receptors, including CCR8, and actively home to CCL8 deposits located around the airway epithelium. Within lung tissue, ILC2s were particularly motile in extracellular matrix–enriched regions. We show that collagen-I drives ILC2 to markedly change their morphology by remodeling their actin cytoskeleton to promote environmental exploration critical for regulating eosinophilic inflammation. Our study provides previously unappreciated insights into ILC2 migratory patterns during inflammation and highlights the importance of environmental guidance cues in the lung in controlling ILC2 dynamics.

scholarly journals The Fate of Activated Group 2 Innate Lymphoid Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Mathä ◽  
Itziar Martinez-Gonzalez ◽  
Catherine A. Steer ◽  
Fumio Takei
Keyword(s):  
Stromal Cells ◽  
Inflammatory Diseases ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
First Line ◽  
The Past ◽  
Mucosal Tissues ◽  
Group 2 ◽  
Type 2 Inflammation

Group 2 innate lymphoid cells (ILC2s) reside in both mucosal and non-mucosal tissues and play critical roles in the first line of defense against parasites and irritants such as allergens. Upon activation by cytokines released from epithelial and stromal cells during tissue damage or stimulation, ILC2s produce copious amounts of IL-5 and IL-13, leading to type 2 inflammation. Over the past 10 years, ILC2 involvement in a variety of human diseases has been unveiled. However, questions remain as to the fate of ILC2s after activation and how that might impact their role in chronic inflammatory diseases such as asthma and fibrosis. Here, we review studies that have revealed novel properties of post-activation ILC2s including the generation of immunological memory, exhausted-like phenotype, transdifferentiation and activation-induced migration.

scholarly journals Migration of Lung Resident Group 2 Innate Lymphoid Cells Link Allergic Lung Inflammation and Liver Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Mathä ◽  
Mónica Romera-Hernández ◽  
Catherine A. Steer ◽  
Yi Han Yin ◽  
Mona Orangi ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Eosinophilic Inflammation ◽  
Allergic Lung Inflammation ◽  
Pre Treatment ◽  
Group 2 ◽  
Resident Group ◽  
Type 2 Inflammation

Group 2 innate lymphoid cells (ILC2s) are tissue resident in the lung and activated by inhaled allergens via epithelial-derived alarmins including IL-33. Activated ILC2s proliferate, produce IL-5 and IL-13, and induce eosinophilic inflammation. Here, we report that intranasal IL-33 or the protease allergen papain administration resulted in increased numbers of ILC2s not only in the lung but also in peripheral blood and liver. Analyses of IL-33 treated parabiosis mice showed that the increase in lung ILC2s was due to proliferation of lung resident ILC2s, whereas the increase in liver ILC2s was due to the migration of activated lung ILC2s. Lung-derived ILC2s induced eosinophilic hepatitis and expression of fibrosis-related genes. Intranasal IL-33 pre-treatment also attenuated concanavalin A-induced acute hepatitis and cirrhosis. These results suggest that activated lung resident ILC2s emigrate from the lung, circulate, settle in the liver and promote type 2 inflammation and attenuate type 1 inflammation.

scholarly journals Cyclic-di-GMP induces STING-dependent ILC2 to ILC1 shift during innate type 2 lung inflammation

2020 ◽  
Author(s):  
Kellen J. Cavagnero ◽  
Jana H. Badrani ◽  
Luay H. Naji ◽  
Michael B. Amadeo ◽  
Anthea S. Leng ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Bacterial Colonization ◽  
Lymphoid Cells ◽  
Group 2 ◽  
Viral Responses ◽  
Type 2 Inflammation

ABSTRACTType 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed both lung proliferating CD127+ST2+ ILC2s and Alternaria- and IL-33-induced lung inflammation. Further, transcriptomic analysis of CD127−ST2− Thy1.2+ ILCs, which were expanded and activated by CDG, revealed an ILC1 signature. CDG administration led to accumulation of IFNγ+ and T-bet+ ILC1s, as well as neutrophilia, independent of IL-18R, IL-12, and STAT6 but dependent on stimulator of interferon genes (STING) and partially dependent on type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.

scholarly journals Cyclic-di-GMP Induces STING-Dependent ILC2 to ILC1 Shift During Innate Type 2 Lung Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kellen J. Cavagnero ◽  
Jana H. Badrani ◽  
Luay H. Naji ◽  
Michael B. Amadeo ◽  
Anthea S. Leng ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Bacterial Colonization ◽  
Lymphoid Cells ◽  
Group 2 ◽  
Viral Responses ◽  
Type 2 Inflammation

Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that intranasal CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed CD127+ST2+ ILC2s and type 2 lung inflammation during Alternaria and IL-33 exposure. Further, CD127–ST2–Thy1.2+ lung ILCs, which showed a transcriptomic signature consistent with ILC1s, were expanded and activated by CDG combined with either Alternaria or IL-33. CDG-mediated suppression of type 2 inflammation occurred independent of IL-18R, IL-12, and STAT6 but required the stimulator of interferon genes (STING) and type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.

scholarly journals Tissue signals imprint Aiolos expression in ILC2s to modulate type 2 immunity

2021 ◽  
Author(s):  
Jinxin Qiu ◽  
Jingjing Zhang ◽  
Yan Ji ◽  
Hanxiao Sun ◽  
Zhitao Gu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Lymphoid Cells ◽  
Open Chromatin ◽  
Tissue Microenvironment ◽  
Aryl Hydrocarbon ◽  
Group 2 ◽  
Human And Mouse ◽  
Type 2 Inflammation ◽  
Pro Inflammatory Cytokines

AbstractGroup 2 innate lymphoid cells (ILC2s) manifest tissue heterogeneity and are crucial modulators of regional immune responses. The molecular mechanisms regulating tissue ILC2 properties remain elusive. Here, we interrogate the signatures of ILC2s from five tissues at the transcriptome and epigenetic level. We have found that tissue microenvironment strongly shapes ILC2 identities. The intestine induces Aiolos+ILC2s, whereas lung and pancreas enhance Galectin-1+ILC2s. Though being a faithful gut ILC2 feature under the steady state, Aiolos is induced in non-intestinal ILC2s by pro-inflammatory cytokines. Specifically, IL-33 stimulates Aiolos expression in both human and mouse non-intestinal ILC2s. Functionally, Aiolos facilitates eosinophil recruitment by supporting IL-5 production and proliferation of ST2+ILC2s through inhibiting PD-1. At the epigenetic level, ILC2 tissue characters are imprinted by open chromatin regions (OCRs) at non-promoters. Intestinal-specific transcription factor aryl hydrocarbon receptor (Ahr) binds to Ikzf3 (encoding Aiolos) locus, increases the accessibility of an intestinal ILC2-specific OCR, and promotes the Ikzf3 transcription by enhancing H3K27ac. Consequently, Ahr prevents ILC2s entering an “exhausted-like” state through sustaining Aiolos expression. Our work elucidates mechanism of ILC2 tissue adaptation and highlights Aiolos as a potential target of type 2 inflammation.

scholarly journals Activation of group 2 innate lymphoid cells exacerbates and confers corticosteroid resistance to mouse nasal type 2 inflammation

2017 ◽  
Vol 29 (5) ◽  
pp. 221-233 ◽  
Author(s):  
Taiyo Morikawa ◽  
Ayumi Fukuoka ◽  
Kazufumi Matsushita ◽  
Koubun Yasuda ◽  
Naruhito Iwasaki ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Nasal Type ◽  
Corticosteroid Resistance ◽  
Group 2 ◽  
Type 2 Inflammation

Role of TNFSF11 and Group 2 Innate Lymphoid Cells in Type 2 Inflammation in Chronic Rhinosinusitis with Nasal Polyps

2018 ◽  
Vol 141 (2) ◽  
pp. AB1 ◽  
Author(s):  
Noriko Ogasawara ◽  
Julie A. Poposki ◽  
Aiko I. Klingler ◽  
Bruce K. Tan ◽  
Kathryn E. Hulse ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2 ◽  
Type 2 Inflammation
Sign in / Sign up

Export Citation Format

Share Document