scholarly journals Dichotomous metabolic networks govern human ILC2 proliferation and function

2021 ◽  
Author(s):  
Laura Surace ◽  
Jean-Marc Doisne ◽  
Carys A. Croft ◽  
Anna Thaller ◽  
Pedro Escoll ◽  
...  
Keyword(s):  
Amino Acids ◽  
Metabolic Networks ◽  
Mammalian Target Of Rapamycin ◽  
Immune Defense ◽  
Lymphoid Cells ◽  
Interleukin 33 ◽  
Type 2 Cytokines ◽  
Group 2 ◽  
And Function

AbstractGroup 2 innate lymphoid cells (ILC2s) represent innate homologs of type 2 helper T cells (TH2) that participate in immune defense and tissue homeostasis through production of type 2 cytokines. While T lymphocytes metabolically adapt to microenvironmental changes, knowledge of human ILC2 metabolism is limited, and its key regulators are unknown. Here, we show that circulating ‘naive’ ILC2s have an unexpected metabolic profile with a higher level of oxidative phosphorylation (OXPHOS) than natural killer (NK) cells. Accordingly, ILC2s are severely reduced in individuals with mitochondrial disease (MD) and impaired OXPHOS. Metabolomic and nutrient receptor analysis revealed ILC2 uptake of amino acids to sustain OXPHOS at steady state. Following activation with interleukin-33 (IL-33), ILC2s became highly proliferative, relying on glycolysis and mammalian target of rapamycin (mTOR) to produce IL-13 while continuing to fuel OXPHOS with amino acids to maintain cellular fitness and proliferation. Our results suggest that proliferation and function are metabolically uncoupled in human ILC2s, offering new strategies to target ILC2s in disease settings.

scholarly journals ICAM-1 controls development and function of ILC2

2018 ◽  
Vol 215 (8) ◽  
pp. 2157-2174 ◽  
Author(s):  
Ai-Hua Lei ◽  
Qiang Xiao ◽  
Gao-Yu Liu ◽  
Kun Shi ◽  
Qiong Yang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Lymphoid Cells ◽  
Peripheral Tissues ◽  
Type 2 Cytokines ◽  
Functionally Impaired ◽  
Group 2 ◽  
And Function

Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1–deficient (ICAM-1−/−) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from ICAM-1−/− mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in ICAM-1−/− mice after administration of papain or Alternaria alternata. We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.

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 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.

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.

scholarly journals TNF Induces the Production of Type 2 Cytokines in Human Group 2 Innate Lymphoid Cells

2019 ◽  
Vol 143 (2) ◽  
pp. AB1
Author(s):  
Atsushi Kato ◽  
Noriko Ogasawara ◽  
Julie A. Poposki ◽  
Aiko I. Klingler ◽  
Kathryn E. Hulse ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Human Group ◽  
Type 2 Cytokines ◽  
Group 2

scholarly journals IL-10 Prevents the Production of Type 2 Cytokines in Human Group 2 Innate Lymphoid Cells

2017 ◽  
Vol 139 (2) ◽  
pp. AB14
Author(s):  
Noriko Ogasawara ◽  
Julie A. Poposki ◽  
Aiko I. Klingler ◽  
Bruce K. Tan ◽  
Kathryn E. Hulse ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Human Group ◽  
Type 2 Cytokines ◽  
Group 2

scholarly journals c-Rel Is Required for IL-33-Dependent Activation of ILC2s

2021 ◽  
Vol 12 ◽  
Author(s):  
Aidil Zaini ◽  
Thomas S. Fulford ◽  
Raelene J. Grumont ◽  
Jessica Runting ◽  
Grace Rodrigues ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Cytokine Production ◽  
Control Point ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Central Control ◽  
Critical Component ◽  
Interleukin 33 ◽  
Group 2 ◽  
And Function

Group 2 innate lymphoid cells (ILC2s) are emerging as important cellular regulators of homeostatic and disease-associated immune processes. The cytokine interleukin-33 (IL-33) promotes ILC2-dependent inflammation and immunity, with IL-33 having been shown to activate NF-κB in a wide variety of cell types. However, it is currently unclear which NF-κB members play an important role in IL-33-dependent ILC2 biology. Here, we identify the NF-κB family member c-Rel as a critical component of the IL-33-dependent activation of ILC2s. Although c-Rel is dispensable for ILC2 development, it is critical for ILC2 function in the lung, with c-Rel-deficient (c-Rel–/–) mice present a significantly reduced response to papain- and IL-33-induced lung inflammation. We also show that the absence of c-Rel reduces the IL-33-dependent expansion of ILC2 precursors and lower levels of IL-5 and IL-13 cytokine production by mature ILC2s in the lung. Together, these results identify the IL-33-c-Rel axis as a central control point of ILC2 activation and function.

scholarly journals IL-10, TGF-β, and glucocorticoid prevent the production of type 2 cytokines in human group 2 innate lymphoid cells

2018 ◽  
Vol 141 (3) ◽  
pp. 1147-1151.e8 ◽  
Author(s):  
Noriko Ogasawara ◽  
Julie A. Poposki ◽  
Aiko I. Klingler ◽  
Bruce K. Tan ◽  
Ava R. Weibman ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Human Group ◽  
Type 2 Cytokines ◽  
Group 2

scholarly journals Tissue-specific pathways extrude activated ILC2s to disseminate type 2 immunity

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Roberto R. Ricardo-Gonzalez ◽  
Christoph Schneider ◽  
Chang Liao ◽  
Jinwoo Lee ◽  
Hong-Erh Liang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymphoid Cells ◽  
Nippostrongylus Brasiliensis ◽  
Tissue Specific ◽  
Type 2 Cytokines ◽  
Receptor Profile ◽  
Small Intestinal ◽  
Group 2 ◽  
Specific Tissue

Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells prominent at barrier sites. Although precursors are found in blood, mature ILC2s can enter the circulation after small intestinal perturbation by migratory helminths and move to distant tissues to influence the local reparative response. Using fate-mapping and methods to bypass the lung or intestinal phases of Nippostrongylus brasiliensis infection, we show that blood ILC2s comprise heterogeneous populations derived from distinct tissues that are dependent on alarmins matched to the receptor profile of the specific tissue ILC2s. Activation of local ILC2s by tissue-specific alarmins induced their proliferation, lymph node migration, and blood dissemination, thus systemically distributing type 2 cytokines. These studies uncover a possible mechanism by which local innate responses transition to systemic type 2 responses by extrusion of activated sentinel ILC2s from tissue into the circulation.

scholarly journals TNF induces production of type 2 cytokines in human group 2 innate lymphoid cells

2020 ◽  
Vol 145 (1) ◽  
pp. 437-440.e8 ◽  
Author(s):  
Noriko Ogasawara ◽  
Julie A. Poposki ◽  
Aiko I. Klingler ◽  
Bruce K. Tan ◽  
Kathryn E. Hulse ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Human Group ◽  
Type 2 Cytokines ◽  
Group 2
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