scholarly journals Alveolar macrophages rely on GM-CSF from alveolar epithelial type 2 cells before and after birth

2021 ◽  
Vol 218 (10) ◽  
Author(s):  
Julia Gschwend ◽  
Samantha P.M. Sherman ◽  
Frederike Ridder ◽  
Xiaogang Feng ◽  
Hong-Erh Liang ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Γδ T Cells ◽  
Lymphoid Cells ◽  
Environmental Cues ◽  
Alveolar Epithelial ◽  
Gm Csf ◽  
Proliferation And Differentiation ◽  
Before And After ◽  
Group 2

Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and nonimmune cells and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular cross talk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoietic Csf2 and basophil depletion. Instead, AT2 lineage-specific constitutive and inducible Csf2 deletion revealed the nonredundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.

scholarly journals Alveolar macrophages strictly rely on GM-CSF from alveolar epithelial type 2 cells before and after birth

2021 ◽  
Author(s):  
Julia Gschwend ◽  
Samantha P.M. Sherman ◽  
Frederike Ridder ◽  
Xiaogang Feng ◽  
Hong-Erh Liang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Alveolar Macrophages ◽  
Γδ T Cells ◽  
Lymphoid Cells ◽  
Alveolar Epithelial ◽  
Gm Csf ◽  
Proliferation And Differentiation ◽  
Before And After ◽  
Group 2

Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and non-immune cells, and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular crosstalk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoietic Csf2 and basophil depletion. Instead, AT2 lineage-specific constitutive and inducible Csf2 deletion revealed the non-redundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.

scholarly journals STING activation in alveolar macrophages and group 2 innate lymphoid cells suppresses IL-33-driven type 2 immunopathology

JCI Insight ◽  
2021 ◽  
Author(s):  
Li She ◽  
Gema D. Barrera ◽  
Liping Yan ◽  
Hamad Hazzaa Alanazi ◽  
Edward G. Brooks ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

scholarly journals Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma

2021 ◽  
Vol 22 (9) ◽  
pp. 4369
Author(s):  
Corrado Pelaia ◽  
Giulia Pelaia ◽  
Claudia Crimi ◽  
Angelantonio Maglio ◽  
Luca Gallelli ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Airway Epithelial Cells ◽  
Lymphoid Cells ◽  
Airway Epithelial ◽  
Airborne Pollutants ◽  
Group 2 ◽  
Efficacy Profile ◽  
Refractory Asthma

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

scholarly journals Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis

2020 ◽  
Vol 32 (6) ◽  
pp. 407-419 ◽  
Author(s):  
Yurina Miyajima ◽  
Kafi N Ealey ◽  
Yasutaka Motomura ◽  
Miho Mochizuki ◽  
Natsuki Takeno ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Adipocyte Differentiation ◽  
Allergic Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Brown Adipocytes ◽  
Morphogenetic Protein ◽  
Group 2

Abstract Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is still unclear. Here, we report on the role of ILC2-derived bone morphogenetic protein 7 (BMP7) in adipocyte differentiation and lipid accumulation. Co-culture of fat-derived ILC2s with pluripotent mesenchymal C3H10T1/2 cells and committed white preadipocyte 3T3-L1 cells resulted in their differentiation to adipocytes and induced lipid accumulation. Co-culture experiments using BMP7-deficient ILC2s revealed that BMP7, produced by ILC2s, induces differentiation into brown adipocytes. Our results demonstrate that BMP7, produced by ILC2s, affects adipocyte differentiation, particularly in brown adipocytes.

scholarly journals Group 2 Innate Lymphoid Cells: Central Players in a Recurring Theme of Repair and Regeneration

2020 ◽  
Vol 21 (4) ◽  
pp. 1350 ◽  
Author(s):  
Melina Messing ◽  
Sia Cecilia Jan-Abu ◽  
Kelly McNagny
Keyword(s):  
T Regulatory Cells ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Helminth Infections ◽  
Neonatal Immunity ◽  
Group 2 ◽  
Transcription Factor Expression

Innate lymphoid cells (ILCs) are recently discovered innate counterparts to the well-established T helper cell subsets and are most abundant at barrier surfaces, where they participate in tissue homeostasis and inflammatory responses against invading pathogens. Group 2 innate lymphoid cells (ILC2s) share cytokine and transcription factor expression profiles with type-2 helper T cells and are primarily associated with immune responses against allergens and helminth infections. Emerging data, however, suggests that ILC2s are also key regulators in other inflammatory settings; both in a beneficial context, such as the establishment of neonatal immunity, tissue repair, and homeostasis, and in the context of pathological tissue damage and disease, such as fibrosis development. This review focuses on the interactions of ILC2s with stromal cells, eosinophils, macrophages, and T regulatory cells that are common to the different settings in which type-2 immunity has been explored. We further discuss how an understanding of these interactions can reveal new avenues of therapeutic tissue regeneration, where the role of ILC2s is yet to be fully established.

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.

Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells

2015 ◽  
Vol 17 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Claudia U Duerr ◽  
Connor D A McCarthy ◽  
Barbara C Mindt ◽  
Manuel Rubio ◽  
Alexandre P Meli ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Type I ◽  
Group 2
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