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 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 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 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 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.

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 A CCL1/CCR8-dependent feed-forward mechanism drives ILC2 functions in type 2–mediated inflammation

2019 ◽  
Vol 216 (12) ◽  
pp. 2763-2777 ◽  
Author(s):  
Lisa Knipfer ◽  
Anja Schulz-Kuhnt ◽  
Markus Kindermann ◽  
Vicky Greif ◽  
Cornelia Symowski ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Inflammatory Diseases ◽  
Lymphoid Cells ◽  
Immune Functions ◽  
In Vivo Experiments ◽  
Anatomical Compartment ◽  
Group 2

Group 2 innate lymphoid cells (ILC2s) possess indispensable roles during type 2–mediated inflammatory diseases. Although their physiological and detrimental immune functions seem to depend on the anatomical compartment they reside, their tissue tropism and the molecular and immunological processes regulating the self-renewal of the local pool of ILC2s in the context of inflammation or infection are incompletely understood. Here, we analyzed the role of the CC-chemokine receptor CCR8 for the biological functions of ILC2s. In vitro and in vivo experiments indicated that CCR8 is in comparison to the related molecule CCR4 less important for migration of these cells. However, we found that activated mouse and human ILC2s produce the CCR8 ligand CCL1 and are a major source of CCL1 in vivo. CCL1 signaling to ILC2s regulates their proliferation and supports their capacity to protect against helminthic infections. In summary, we identify a novel chemokine receptor–dependent mechanism by which ILC2s are regulated during type 2 responses.

Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma

2021 ◽  
Vol 39 (1) ◽  
Author(s):  
Noe Rodriguez-Rodriguez ◽  
Mayuri Gogoi ◽  
Andrew N.J. McKenzie
Keyword(s):  
Allergic Asthma ◽  
Cell Activation ◽  
Innate Lymphoid Cells ◽  
Experimental Models ◽  
Lymphoid Cells ◽  
Annual Review ◽  
Publication Date ◽  
Effector Cytokines ◽  
Group 2

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then disseminating cytokine cues to elicit effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals IL-9–mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation

2013 ◽  
Vol 210 (13) ◽  
pp. 2951-2965 ◽  
Author(s):  
Jan-Eric Turner ◽  
Peter J. Morrison ◽  
Christoph Wilhelm ◽  
Mark Wilson ◽  
Helena Ahlfors ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Damage Control ◽  
Recovery Phase ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Nippostrongylus Brasiliensis

IL-9 fate reporter mice established type 2 innate lymphoid cells (ILC2s) as major producers of this cytokine in vivo. Here we focus on the role of IL-9 and ILC2s during the lung stage of infection with Nippostrongylus brasiliensis, which results in substantial tissue damage. IL-9 receptor (IL-9R)–deficient mice displayed reduced numbers of ILC2s in the lung after infection, resulting in impaired IL-5, IL-13, and amphiregulin levels, despite undiminished numbers of Th2 cells. As a consequence, the restoration of tissue integrity and lung function was strongly impaired in the absence of IL-9 signaling. ILC2s, in contrast to Th2 cells, expressed high levels of the IL-9R, and IL-9 signaling was crucial for the survival of activated ILC2s in vitro. Furthermore, ILC2s in the lungs of infected mice required the IL-9R to up-regulate the antiapoptotic protein BCL-3 in vivo. This highlights a unique role for IL-9 as an autocrine amplifier of ILC2 function, promoting tissue repair in the recovery phase after helminth-induced lung inflammation.

scholarly journals Group 2 Innate Lymphoid Cells (ILC2): Type 2 Immunity and Helminth Immunity

2019 ◽  
Vol 20 (9) ◽  
pp. 2276 ◽  
Author(s):  
De’Broski Herbert ◽  
Bonnie Douglas ◽  
Kelly Zullo
Keyword(s):  
Cell Lineage ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Helminth Parasites ◽  
Cell Recruitment ◽  
Distinct Cell ◽  
Health And Disease ◽  
Group 2 ◽  
Unique Cell

Group 2 innate lymphoid cells (ILC2) have emerged as a major component of type 2 inflammation in mice and humans. ILC2 secrete large amounts of interleukins 5 and 13, which are largely responsible for host protective immunity against helminth parasites because these cytokines induce profound changes in host physiology that include: goblet cell metaplasia, mucus accumulation, smooth muscle hypercontractility, eosinophil and mast cell recruitment, and alternative macrophage activation (M2). This review covers the initial recognition of ILC2 as a distinct cell lineage, the key studies that established their biological importance, particularly in helminth infection, and the new directions that are likely to be the focus of emerging work that further explores this unique cell population in the context of health and disease.

scholarly journals Non-canonical Activation of Human Group 2 Innate Lymphoid Cells by TLR4 Signaling

2020 ◽  
Author(s):  
Li She ◽  
Hamad H. Alanazi ◽  
Jingwei Wang ◽  
Daniel P. Chupp ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cd40 Ligand ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Large Set ◽  
Humanized Mouse Model ◽  
Tlr4 Signaling ◽  
Type 2 Immunity ◽  
Effector Cytokines ◽  
Group 2

AbstractGroup 2 innate lymphoid cells (ILC2) are emerging as a critical player in type 2 immunity at barrier sites in response to microbial infections and allergen exposures. Although their classical activators are known to be host epithelial-derived alarmin cytokines IL-33, IL-25 or TSLP, it remains elusive whether ILC2 cells can be activated by directly sensing microbial ligands via pattern-recognition receptors such as toll-like receptors (TLRs). Here we report that toll-like receptor 4 (TLR4) is a potent activating receptor of human ILC2. We found that among many microbial ligands examined, lipopolysaccharides (LPS) from multiple species of Gram-negative bacteria, was found to potently stimulate human, but not murine ILC2, to proliferate and produce massive amounts of type 2 effector cytokines IL-4, IL-5, and IL-13. LPS-activated ILC2 also had greatly enhanced the CD40 ligand (CD154) expression and were able to promote the proliferation and antibody production of human B cells in culture. In a humanized mouse model, LPS activated the adoptively transferred human ILC2 in mouse lungs. Both NF-kB and JAK pathways, but not the IL-33-ST2 pathway, were required for LPS to activate human ILC2. RNA-seq data further revealed that LPS induced a large set of genes overlapped significantly with those induced by IL-33. Collectively, these findings support a non-classical mode of activating human ILC2 cells via the LPS-TLR4 signaling axis. Thus, targeting TLR4 signaling pathway might be developed as a new approach by modulating ILC2 activation in treating various type 2 immunity-associated diseases.

Sign in / Sign up

Export Citation Format

Share Document