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 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 Interferon-γconstrains cytokine production of group 2 innate lymphoid cells

Immunology ◽  
2015 ◽  
Vol 147 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Fujimi Kudo ◽  
Masashi Ikutani ◽  
Yoichi Seki ◽  
Takeshi Otsubo ◽  
Yuki I. Kawamura ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

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 PD-1 regulates KLRG1+ group 2 innate lymphoid cells

2017 ◽  
Vol 214 (6) ◽  
pp. 1663-1678 ◽  
Author(s):  
Samuel Taylor ◽  
Yuefeng Huang ◽  
Grace Mallett ◽  
Chaido Stathopoulou ◽  
Tania C. Felizardo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Burden ◽  
Innate Lymphoid Cells ◽  
Cell Number ◽  
Lymphoid Cells ◽  
Negative Regulator ◽  
Intrinsic Defect ◽  
Nippostrongylus Brasiliensis ◽  
Important Negative Regulator ◽  
Group 2

Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator of KLRG1+ ILC-2 function in both mice and humans. Increase in KLRG1+ ILC-2 cell numbers was attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred in Pdcd1−/− mice and, upon adoptive transfer, Pdcd1−/− KLRG1+ ILC-2s significantly reduced worm burden. Furthermore, blocking PD-1 with an antibody increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore, PD-1 is required for maintaining the number, and hence function, of KLRG1+ ILC-2s.

scholarly journals The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo

2020 ◽  
Vol 18 (1) ◽  
pp. 230-242 ◽  
Author(s):  
Lei Zhang ◽  
Yuanlin Ying ◽  
Shuqiu Chen ◽  
Preston R. Arnold ◽  
Fafa Tian ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2 ◽  
Immune Pathology

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 Female and male mouse lung group 2 innate lymphoid cells differ in gene expression profiles and cytokine production

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0214286 ◽  
Author(s):  
Laura Mathä ◽  
Hanjoo Shim ◽  
Catherine A. Steer ◽  
Yi Han Yin ◽  
Itziar Martinez-Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Male Mouse ◽  
Cytokine Production ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Mouse Lung ◽  
Group 2

scholarly journals IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent

2021 ◽  
Vol 6 (59) ◽  
pp. eabe5084
Author(s):  
Clare S. Hardman ◽  
Yi-Ling Chen ◽  
Maryam Salimi ◽  
Janina Nahler ◽  
Daniele Corridoni ◽  
...  
Keyword(s):  
Muramyl Dipeptide ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Interleukin 5 ◽  
Direct Sensing ◽  
Specific Receptors ◽  
Group 2 ◽  
Bacterial Sensing

Cutaneous group 2 innate lymphoid cells (ILC2) are spatially and epigenetically poised to respond to barrier compromise and associated immunological threats. ILC2, lacking rearranged antigen-specific receptors, are primarily activated by damage-associated cytokines and respond with type 2 cytokine production. To investigate ILC2 potential for direct sensing of skin pathogens and allergens, we performed RNA sequencing of ILC2 derived from in vivo challenged human skin or blood. We detected expression of NOD2 and TLR2 by skin and blood ILC2. Stimulation of ILC2 with TLR2 agonist alone not only induced interleukin-5 (IL-5) and IL-13 expression but also elicited IL-6 expression in combination with Staphylococcus aureus muramyl dipeptide (MDP). Heat-killed skin-resident bacteria provoked an IL-6 profile in ILC2 in vitro that was notably impaired in ILC2 derived from patients with nucleotide-binding oligomerization domain-containing protein 2 (NOD2) mutations. In addition, we show that NOD2 signaling can stimulate autophagy in ILC2, which was also impaired in patients with NOD2 mutations. Here, we have identified a role for ILC2 NOD2 signaling in the differential regulation of ILC2-derived IL-6 and have reported a previously unrecognized pathway of direct ILC2 bacterial sensing.

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