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 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.

Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses

2015 ◽  
Vol 17 (1) ◽  
pp. 76-86 ◽  
Author(s):  
Kazuyo Moro ◽  
Hiroki Kabata ◽  
Masanobu Tanabe ◽  
Satoshi Koga ◽  
Natsuki Takeno ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Lymphoid Cells ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Responses ◽  
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 Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Markus Kindermann ◽  
Lisa Knipfer ◽  
Stephanie Obermeyer ◽  
Uwe Müller ◽  
Gottfried Alber ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Pulmonary Cryptococcosis ◽  
Group 2

Regulating the development of pulmonary Group 2 innate lymphoid cells

2019 ◽  
Vol 400 (11) ◽  
pp. 1497-1507 ◽  
Author(s):  
Sofia Helfrich ◽  
Claudia U. Duerr
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Morphological Changes ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
The Family ◽  
Intrinsic Regulation ◽  
Group 2 ◽  
And Function

Abstract Group 2 innate lymphoid cells (ILC2s) are members of the family of innate lymphoid cells and are innately committed to type 2 immune responses. In the lungs, ILC2s are the predominant population of innate lymphoid cells (ILCs) and their development is orchestrated by several different transcription factors ensuring lineage commitment by intrinsic regulation. ILC2s are present in the lungs from the foetal period onwards and are thus exposed to extrinsic regulation due to the airways’ continuous morphological changes upon birth. In this review, we will briefly summarise the dependence of ILC2s on transcription factors and discuss recently described characteristics and function of early life ILC2s in the lungs.

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