scholarly journals The Intestine-lung Trafficking of Memory-like Group 2 Innate Lymphoid Cells Orchestrates Asthma Relapse

2021 ◽  
Author(s):  
Kaifan Bao ◽  
Yijing Zhou ◽  
Yanyan Chen ◽  
Meiling Wang ◽  
Weiyuan Yuan ◽  
...  
Keyword(s):  
Small Intestine ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Immune Memory ◽  
Circulating Cells ◽  
Adaptive Immune Cells ◽  
Group 2 ◽  
Molecular Bases

Background: Recent works imply that immune memory might be expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases are largely unknown. Here, we investigated the memory and migrating properties of Lin KLRG1 IL-17RB ILC2s (herein referred as mILC2s) and their contribution to asthma relapse. Methods: Clinical asthmatic subjects and HDM-induced mice asthma models were applied to investigate the memory-like characteristics of mILC2s including greater effector cytokine-producing potential and in vivo persistence. Parabiosis pairs of CD45.1 and CD45.2 mice were employed to determine whether mILC2s were circulating cells. Adoptive transplantation was performed to analyze the origin of the mILC2s accumulated in airway upon asthma relapse. CCR9 and S1P signaling blockade were used to confirm the migration of mILC2s during different asthma phases by In vivo imaging. KLRG1 neutralization was utilized to analyze the role of mILC2s in asthma relapse on Rag1 mice. Results: mILC2s persisted in vivo and retained the potency of producing IL-13 and re-inducing allergic responses. Critically, parabiosis study and in vivo imaging showed that the vast majority of mILC2s migrated to and resided in small intestine during asthma remission, and subsequently moved to airway upon re-encountering antigens, regulated by CCR9 and S1P signaling. Blockade of S1P signaling markedly limited secondary exposure-induced airway inflammation. Furthermore, KLRG1 neutralization attenuated asthmatic responses of Rag1 mice, supporting a pivotal role for mILC2s in mediating asthma relapse independent of adaptive immune cells. Conclusion: mILC2s exhibit memory-like and lung-small intestine migratory properties, which empowers them to drive asthma relapse.

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 Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Ivan Ting Hin Fung ◽  
Poornima Sankar ◽  
Yuanyue Zhang ◽  
Lisa S. Robison ◽  
Xiuli Zhao ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Brain Physiology ◽  
Aged Brain ◽  
Group 2 ◽  
Resident Group ◽  
And Function

Increasing evidence has challenged the traditional view about the immune privilege of the brain, but the precise roles of immune cells in regulating brain physiology and function remain poorly understood. Here, we report that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the choroid plexus of aged brains. ILC2 in the aged brain are long-lived, are relatively resistant to cellular senescence and exhaustion, and are capable of switching between cell cycle dormancy and proliferation. They are functionally quiescent at homeostasis but can be activated by IL-33 to produce large amounts of type 2 cytokines and other effector molecules in vitro and in vivo. Intracerebroventricular transfer of activated ILC2 revitalized the aged brain and enhanced the cognitive function of aged mice. Administration of IL-5, a major ILC2 product, was sufficient to repress aging-associated neuroinflammation and alleviate aging-associated cognitive decline. Targeting ILC2 in the aged brain may provide new avenues to combat aging-associated neurodegenerative disorders.

scholarly journals Immune checkpoints on innate lymphoid cells

2017 ◽  
Vol 214 (6) ◽  
pp. 1561-1563 ◽  
Author(s):  
Laura Chiossone ◽  
Eric Vivier
Keyword(s):  
Cytokine Production ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Negative Regulator ◽  
Immune Checkpoints ◽  
Group 2 ◽  
Blocking Antibodies

In this issue of JEM, Taylor et al. (https://doi.org/10.1084/jem.20161653) describe PD-1 as a critical negative regulator of group 2 innate lymphoid cells (ILC-2s). PD-1 intrinsically controls proliferation and cytokine production of both mouse and human ILC-2s. PD-1 signaling inhibits STAT5 phosphorylation and the removal of this brake by knocking down PD-1 expression or by using anti–PD-1 blocking antibodies, translated in vivo into better clearance of helminth worm infection in mice.

scholarly journals IL-27 suppresses type 2 immune responses in vivo via direct effects on group 2 innate lymphoid cells

2016 ◽  
Vol 9 (6) ◽  
pp. 1384-1394 ◽  
Author(s):  
T Mchedlidze ◽  
M Kindermann ◽  
A T Neves ◽  
D Voehringer ◽  
M F Neurath ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Direct Effects ◽  
Group 2

scholarly journals Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

2021 ◽  
Vol 6 (57) ◽  
pp. eabd0359
Author(s):  
Luke B. Roberts ◽  
Corinna Schnoeller ◽  
Rita Berkachy ◽  
Matthew Darby ◽  
Jamie Pillaye ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Mucosal Barrier ◽  
Nippostrongylus Brasiliensis ◽  
Interleukin 33 ◽  
Group 2 ◽  
Maximal Induction

Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize and release acetylcholine (ACh) during parasitic nematode infection. The cholinergic phenotype of pulmonary ILC2s was associated with their activation state, could be induced by in vivo exposure to extracts of Alternaria alternata or the alarmin cytokines interleukin-33 (IL-33) and IL-25, and was augmented by IL-2 in vitro. Genetic disruption of ACh synthesis by murine ILC2s resulted in increased parasite burdens, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.

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 An ST2-dependent role of bone marrow-derived group 2 innate lymphoid cells in pulmonary fibrosis

2018 ◽  
Vol 245 (4) ◽  
pp. 399-409 ◽  
Author(s):  
Yuyue Zhao ◽  
Francina Gonzalez De Los Santos ◽  
Zhe Wu ◽  
Tianju Liu ◽  
Sem H Phan
Keyword(s):  
Bone Marrow ◽  
Pulmonary Fibrosis ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

The Role of the TL1A/DR3 Axis in the Activation of Group 2 Innate Lymphoid Cells in Subjects with Eosinophilic Asthma

2020 ◽  
Vol 202 (8) ◽  
pp. 1105-1114 ◽  
Author(s):  
Kentaro Machida ◽  
Michael Aw ◽  
Brittany M. A. Salter ◽  
Xiaotian Ju ◽  
Manali Mukherjee ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Eosinophilic Asthma ◽  
Group 2

scholarly journals T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Jan-Hendrik Schroeder ◽  
Katrin Meissl ◽  
Dominika Hromadová ◽  
Jonathan W. Lo ◽  
Joana F. Neves ◽  
...  
Keyword(s):  
Critical Factor ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Mucosal Surfaces ◽  
Specific Pathogen ◽  
Enhanced Expression ◽  
Group 3 ◽  
Deficient Mice

Innate lymphoid cells (ILC) play a significant immunological role at mucosal surfaces such as the intestine. T-bet-expressing group 1 innate lymphoid cells (ILC1) are believed to play a substantial role in inflammatory bowel disease (IBD). However, a role of T-bet-negative ILC3 in driving colitis has also been suggested in mouse models questioning T-bet as a critical factor for IBD. We report here that T-bet deficient mice had a greater cellularity of NKp46-negative ILC3 correlating with enhanced expression of RORγt and IL-7R, but independent of signaling through STAT1 or STAT4. We observed enhanced neutrophilia in the colonic lamina propria (cLP) of these animals, however, we did not detect a greater risk of T-bet-deficient mice to develop spontaneous colitis. Furthermore, by utilizing an in vivo fate-mapping approach, we identified a population of T-bet-positive precursors in NKp46-negative ILC3s. These data suggest that T-bet controls ILC3 cellularity, but does do not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.

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