Metabolic regulation of ILC2 differentiation into ILC1-like cells during<i>Mycobacterium tuberculosis</i>infection

Corral, Dan; Charton, Alison; Krauss, Maria Z; Blanquart, Eve; Levillain, Florence; Lefrançais, Emma; Sneperger, Tamara; Girard, Jean‐Philippe; Eberl, Gérard; Poquet, Yannick; Guéry, Jean‐Charles; Argüello, Rafael J.; Hepworth, Matthew R.; Hudrisier, Denis

doi:10.1101/2021.01.19.427257

Cited by 6 publications

(5 citation statements)

References 50 publications

(94 reference statements)

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“…Indeed, corral et al ( 75), (unpublished) demonstrated that ILC1-like-IFN-g producing cells that expressed little to no classical ILC2 markers emerged during Mtb infection. The authors further illustrated that metabolic environment inhibits ILC2 while augmenting ILC1like-IFN-g producing cells (75). The current study did not assess for the origin of ILC1 and IFN-g production, therefore did not evaluate ILC2 and ILC3 plasticity.…”

Section: Discussionmentioning

confidence: 86%

Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

et al. 2021

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BackgroundType 2 diabetes mellitus (T2DM) is a major risk factor for the acquisition of latent tuberculosis (TB) infection (LTBI) and development of active tuberculosis (ATB), although the immunological basis for this susceptibility remains poorly characterised. Innate lymphoid cells (ILCs) immune responses to TB infection in T2DM comorbidity is anticipated to be reduced. We compared ILC responses (frequency and cytokine production) among adult patients with LTBI and T2DM to patients (13) with LTBI only (14), T2DM only (10) and healthy controls (11).MethodsUsing flow cytometry, ILC phenotypes were categorised based on (Lin−CD127+CD161+) markers into three types: ILC1 (Lin−CD127+CD161+CRTH2-CD117−); ILC2 (Lin−CD127+CD161+CRTH2+) and ILC3 (Lin−CD127+CD161+CRTH2−NKp44+/−CD117+). ILC responses were determined using cytokine production by measuring percentage expression of interferon-gamma (IFN-γ) for ILC1, interleukin (IL)-13 for ILC2, and IL-22 for ILC3. Glycaemic control among T2DM patients was measured using glycated haemoglobin (HbA1c) levels. Data were analysed using FlowJo version 10.7.1, and GraphPad Prism version 8.3.ResultsCompared to healthy controls, patients with LTBI and T2DM had reduced frequencies of ILC2 and ILC3 respectively (median (IQR): 0.01 (0.005-0.04) and 0.002 (IQR; 0.002-0.007) and not ILC1 (0.04 (0.02-0.09) as expected. They also had increased production of IFN-γ [median (IQR): 17.1 (5.6-24.9)], but decreased production of IL-13 [19.6 (12.3-35.1)]. We however found that patients with T2DM had lower ILC cytokine responses in general but more marked for IL-22 production (median (IQR): IFN-γ 9.3 (4.8-22.6); IL-13 22.2 (14.7-39.7); IL-22 0.7 (IQR; 0.1-2.1) p-value 0.02), which highlights the immune suppression status of T2DM. We also found that poor glycaemic control altered ILC immune responses.ConclusionThis study demonstrates that LTBI and T2DM, and T2DM were associated with slight alterations of ILC immune responses. Poor T2DM control also slightly altered these ILC immune responses. Further studies are required to assess if these responses recover after treatment of either TB or T2DM.

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Section: Discussionmentioning

confidence: 86%

Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

et al. 2021

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“…This could be due to alterations in the microenvironment that affect ILC plasticity. Tissue-resident ILCs sense and adapt to environmental changes, and ILCs can adopt new phenotypic and functional profiles [3,34].…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cell Vaccines Impact the Type 2 Innate Lymphoid Cell Population and Their Cytokine Generation in Mice

Chan,

Mehrani,

Minott

et al. 2023

Vaccines

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Dendritic cell (DC) vaccines can stimulate the immune system to target cancer antigens, making them a promising therapy in immunotherapy. Clinical trials have shown limited effectiveness of DC vaccines, highlighting the need to enhance the immune responses they generate. Innate lymphoid cells (ILCs) are a diverse group of innate leukocytes that produce various cytokines and regulate the immune system. These cells have the potential to improve immunotherapies. There is not much research on how group 2 ILCs (ILC2s) communicate with DC vaccines. Therefore, examining the roles of DC vaccination in immune responses is crucial. Our research analyzed the effects of DC vaccination on the ILC2 populations and their cytokine production. By exploring the relationship between ILC2s and DCs, we aimed to understand how this could affect DC-based immunotherapies. The results showed an increase in the number of ILC2s in the local draining lymph node and spleen of tumor-free mice, as well as in the lungs of mice challenged with tumors in a pulmonary metastasis model. This suggests a complex interplay between DC-based vaccines and ILC2s, which is further influenced by the presence of tumors.

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“…Plasticity of ILC2s toward ILC1-like cells was observed in Mycobacterium tuberculosis (Mtb)-infected mice in a pre-print study by Corral et al, which was driven by an upregulation of glycolysis in a HIF-1a-dependent manner (78). Type-1 inflammation induced by Mtb infection, which is recapitulated in vitro by IL-12 and IL-18 stimulation, leads to HIF-1a stabilization in all ILCs subsets in the lung.…”

Section: Ilc2 and Ilc1mentioning

confidence: 98%

“…The induction of an ILC1-like metabolism in ILC2s may drive ILC2s towards an ILC1 phenotype as observed in Mtb-infected mice (Figure 2). This hypothesis is strongly supported by the fact that the conversion of ILC2s into ILC1-like cells and the production of IFN-g was directly dependent on the upregulation of glycolysis (78). Although ILC1-to-ILC2 conversion remains to be formally established, it is perhaps tempting to speculate whether inhibiting glycolysis and boosting OXPHOS in ILC1s (e.g.…”

Section: Ilc2 and Ilc1mentioning

confidence: 99%

“…Type-1 inflammation induced by Mtb infection, which is recapitulated in vitro by IL-12 and IL-18 stimulation, leads to HIF-1a stabilization in all ILCs subsets in the lung. The stabilization of HIF-1a ILC2s has two effects, it upregulates genes associated with an ILC1 phenotype and switches the metabolism of ILC2s toward glycolysis (78). Upon Mtb infection, ILCs present in the lung become activated.…”

Section: Ilc2 and Ilc1mentioning

confidence: 99%

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The Metabolic Basis of ILC Plasticity

Pelletier

Stockmann

2022

Front. Immunol.

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Innate Lymphoid Cells (ILCs) are the innate counterpart of adaptive lymphoid T cells. They are key players in the regulation of tissues homeostasis and early inflammatory host responses. ILCs are divided into three groups, and further subdivided into five subsets, that are characterised by distinct transcription factors, surface markers and their cytokine expression profiles. Group 1 ILCs, including natural killer (NK) cells and non-NK cell ILC1s, express T-bet and produce IFN-γ. Group 2 ILCs depend on GATA3 and produce IL-4, IL-5 and IL-13. Group 3 ILCs, composed of ILC3s and Lymphoid Tissue Inducer (LTi) cells, express RORγt and produce IL-17 and IL-22. Even though, the phenotype of each subset is well defined, environmental signals can trigger the interconversion of phenotypes and the plasticity of ILCs, in both mice and humans. Several extrinsic and intrinsic drivers of ILC plasticity have been described. However, the changes in cellular metabolism that underlie ILC plasticity remain largely unexplored. Given that metabolic changes critically affect fate and effector function of several immune cell types, we, here, review recent findings on ILC metabolism and discuss the implications for ILC plasticity.

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Metabolic regulation of ILC2 differentiation into ILC1-like cells duringMycobacterium tuberculosisinfection

Cited by 6 publications

References 50 publications

Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

Dendritic Cell Vaccines Impact the Type 2 Innate Lymphoid Cell Population and Their Cytokine Generation in Mice

The Metabolic Basis of ILC Plasticity

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