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.

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 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 The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development

2015 ◽  
Vol 212 (6) ◽  
pp. 865-874 ◽  
Author(s):  
Yong Yu ◽  
Cui Wang ◽  
Simon Clare ◽  
Juexuan Wang ◽  
Song-Choon Lee ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Lineage ◽  
Influenza Virus Infection ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Effector Cytokines ◽  
Group 2

Group 2 innate lymphoid cells (ILCs), or ILC2s, are a subset of recently identified ILCs, which play important roles in innate immunity by producing type 2 effector cytokines. Several transcription factors have been found to have critical functions in the development of both ILC2s and T cells. We report here that Bcl11b, a transcription factor essential in T cell lineage commitment and maintenance, is specifically expressed in progenitors committed to the ILC2 lineage and is required for ILC2 development. The Bcl11b gene is expressed in ∼28% of ILC progenitors (ILCPs; common helper innate lymphoid progenitors or ILCPs expressing either ID2 or promyelocytic leukemia zinc finger, respectively). Both in vitro and in vivo, these Bcl11b-expressing early ILCPs generate only ILC2s. Inactivation of Bcl11b causes a complete loss of ILC2 development from hematopoietic progenitors, which is confirmed upon immune challenge with either papain administration or influenza virus infection.

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 The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2

2016 ◽  
Vol 213 (5) ◽  
pp. 687-696 ◽  
Author(s):  
Erin C. Zook ◽  
Kevin Ramirez ◽  
Xiaohuan Guo ◽  
Grant van der Voort ◽  
Mikael Sigvardsson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Messenger Rna ◽  
Critical Factor ◽  
Protective Role ◽  
Lymphoid Cells ◽  
Allergic Lung Inflammation ◽  
Factor Inhibitor ◽  
Group 2

Group 2 innate lymphoid cells (ILC2s) are a subset of ILCs that play a protective role in the response to helminth infection, but they also contribute to allergic lung inflammation. Here, we report that the deletion of the ETS1 transcription factor in lymphoid cells resulted in a loss of ILC2s in the bone marrow and lymph nodes and that ETS1 promotes the fitness of the common progenitor of all ILCs. ETS1-deficient ILC2 progenitors failed to up-regulate messenger RNA for the E protein transcription factor inhibitor ID2, a critical factor for ILCs, and these cells were unable to expand in cytokine-driven in vitro cultures. In vivo, ETS1 was required for the IL-33–induced accumulation of lung ILC2s and for the production of the T helper type 2 cytokines IL-5 and IL-13. IL-25 also failed to elicit an expansion of inflammatory ILC2s when these cells lacked ETS1. Our data reveal ETS1 as a critical regulator of ILC2 expansion and cytokine production and implicate ETS1 in the regulation of Id2 at the inception of ILC2 development.

Human innate lymphoid cells

Blood ◽  
2014 ◽  
Vol 124 (5) ◽  
pp. 700-709 ◽  
Author(s):  
Mette D. Hazenberg ◽  
Hergen Spits
Keyword(s):  
Interferon Γ ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Interleukin 5 ◽  
Type 2 Cytokines ◽  
Lymphoid Tissue Inducer Cells ◽  
Health And Disease ◽  
Group 2 ◽  
And Function ◽  
Regulatory Functions

Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of particular transcription factors for their development and function. Group 1 ILCs (ILC1s) produce interferon γ and depend on Tbet, group 2 ILCs (ILC2s) produce type 2 cytokines like interleukin-5 (IL-5) and IL-13 and require GATA3, and group 3 ILCs (ILC3s) include lymphoid tissue inducer cells, produce IL-17 and/or IL-22, and are dependent on RORγt. Whereas ILCs play essential roles in the innate immune system, uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. In this review, we provide an overview of the characteristics of ILCs in the context of health and disease. We will focus on human ILCs but refer to mouse studies if needed to clarify aspects of ILC biology.

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 Innate lymphoid cells lacking surface expression of CD90 are functional

2021 ◽  
Author(s):  
J-H Schroeder ◽  
T Zabinski ◽  
J F Neves ◽  
GM Lord
Keyword(s):  
Steady State ◽  
Cell Biology ◽  
Surface Expression ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
T Cell Biology ◽  
First Time ◽  
Made In

ABSTRACTHuge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts of T cell biology. As such flow cytometry gating strategies and markers, such as CD90, to identify ILC were discovered. Here we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly some have only a low or even no expression of this marker. CD90-negative CD127+ ILC were identified among all ILC subsets in the gut. CD90-negative cLP ILC2 were frequent at steady state. The frequency of CD90-negative CD127+ ILC was dependent on stimulatory cues in vitro and in vivo, and CD90-negative CD127+ ILC played a functional role as a source of IL-13, IFNγ and IL-17A at steady state and upon dextran sulphate sodium-elicited colitis. Hence, this study highlights for the first time that CD90 is not constitutively expressed by functional ILC in the gut.

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 Effects of Air Pollution on Lung Innate Lymphoid Cells: Review of In Vitro and In Vivo Experimental Studies

2019 ◽  
Vol 16 (13) ◽  
pp. 2347 ◽  
Author(s):  
Bertha Estrella ◽  
Elena N. Naumova ◽  
Magda Cepeda ◽  
Trudy Voortman ◽  
Peter D. Katsikis ◽  
...  
Keyword(s):  
Air Pollution ◽  
Airway Hyperresponsiveness ◽  
Air Pollutants ◽  
Experimental Studies ◽  
Innate Lymphoid Cells ◽  
Diesel Exhaust Particles ◽  
Lymphoid Cells ◽  
Outdoor Air

Outdoor air pollution is associated with respiratory infections and allergies, yet the role of innate lymphoid cells (ILCs) in pathogen containment and airway hyperresponsiveness relevant to effects of air pollutants on ILCs is poorly understood. We conducted a systematic review to evaluate the available evidence on the effect of outdoor air pollutants on the lung type 1 (ILC1) and type 2 ILCs (ILC2) subsets. We searched five electronic databases (up to Dec 2018) for studies on the effect of carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), diesel exhaust particles (DEP), ozone (O3), and particulate matter (PM) on respiratory ILCs. Of 2209 identified citations, 22 full-text papers were assessed for eligibility, and 12 articles describing experimental studies performed in murine strains (9) and on human blood cells (3) were finally selected. Overall, these studies showed that exposure to PM, DEP, and high doses of O3 resulted in a reduction of interferon gamma (IFN-γ) production and cytotoxicity of ILC1. These pollutants and carbon nanotubes stimulate lung ILC2s, produce high levels of interleukin (IL)-5 and IL-13, and induce airway hyperresponsiveness. These findings highlight potential mechanisms by which human ILCs react to air pollution that increase the susceptibility to infections and allergies.

Sign in / Sign up

Export Citation Format

Share Document