Innate Lymphoid Cells in the Induction of Obesity

Sasaki, Takaharu; Moro, Kazuyo; Kubota, Tetsuya; Kubota, Naoto; Kato, Tamotsu; Ohno, Hiroshi; Nakae, Susumu; Saito, Hirohisa; Koyasu, Shigeo

doi:10.1016/j.celrep.2019.06.016

Cited by 75 publications

(79 citation statements)

References 93 publications

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“…However, because of the heterogeneity of group 1 ILCs present in the adipose tissue, the contribution of other tissue-resident group 1 ILCs in obesity-associated insulin resistance remained unknown from these studies. Although recent data indicate a protective role of white adipose tissue ILC2s during homeostasis, ILC2s and ILC3s from the small intestine, but not from white adipose tissue, were found to promote weight gain and insulin resistance during diet-induced obesity in mice [106]. These results suggest that the individual roles of tissue-specific and circulating subsets of ILCs need to be taken into account during obesity.…”

Section: Ilc Activation Disrupts Metabolic Homeostasis During Diet-inmentioning

confidence: 84%

RETRACTED: Living with Yourself: Innate Lymphoid Cell Immunometabolism

Rolot

O’Sullivan

2020

Cells

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Innate lymphoid cells (ILCs) are tissue-resident sentinels of the immune system that function to protect local tissue microenvironments against pathogens and maintain homeostasis. However, because ILCs are sensitively tuned to perturbations within tissues, they can also contribute to host pathology when critical activating signals become dysregulated. Recent work has demonstrated that the crosstalk between ILCs and their environment has a significant impact on host metabolism in health and disease. In this review, we summarize studies that support evidence for the ability of ILCs to influence tissue and systemic metabolism, as well as how ILCs can be regulated by environmental changes in systemic host metabolism. We also highlight studies demonstrating how ILC- intrinsic metabolism influences their activation, proliferation, and homeostasis. Finally, this review discusses the challenges and open questions in the rapidly expanding field of ILCs and immunometabolism.

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Section: Ilc Activation Disrupts Metabolic Homeostasis During Diet-inmentioning

confidence: 84%

RETRACTED: Living with Yourself: Innate Lymphoid Cell Immunometabolism

Rolot

O’Sullivan

2020

Cells

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“…ILC2s provide the first line of defense against helminths and protect the integrity of the epithelium (Artis and Spits, 2015). They are also implicated in the regulation of metabolic homeostasis (Brestoff et al, 2015;Sasaki et al, 2019). Notably, dysregulation of ILC2s has been associated with the development of autoimmune and inflammatory diseases (Cephus et al, 2017;Ealey et al, 2017;Ebbo et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Tumor-Derived Lactic Acid Contributes to the Paucity of Intratumoral ILC2s

et al. 2020

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Graphical AbstractHighlights d ILC2s are involved in eosinophil-associated antitumor responses in melanoma d Lactic acid inhibits function and decreases survival of ILC2s d Tumors with decreased lactic acid production exhibit increased infiltration of ILC2s SUMMARY Group 2 innate lymphoid cells (ILC2s) are abundant in non-lymphoid tissues and increase following infectious and inflammatory insults. In solid tumors, however, ILC2s constitute a relatively small proportion of immune cells. Here, we show, using melanoma as a model, that while the IL-33/IL C2/eosinophil axis suppresses tumor growth, tumor-derived lactate attenuates the function and survival of ILC2s. Melanomas with reduced lactate production (LDHA low ) are growth delayed and typified by an increased number of ILC2s compared with control tumors. Upon IL-33 stimulation, ILC2s accompanied by eosinophils more effectively restrain the growth of LDHA low tumors than control melanomas. Furthermore, database analysis reveals a negative correlation between the expression of LDHA and markers associated with ILC2s and the association of high expression of IL33 and an eosinophil marker SIGLEC8 with better overall survival in human cutaneous melanoma patients. This work demonstrates that the balance between the IL-33/ILC2/eosinophil axis and lactate production by tumor cells regulates melanoma growth.

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“…Future studies are needed to explore the tissue-specific programing of ILC2s in various organs and tissues. A recent study showed that DR3 is expressed on intestinal ILCs, and another group has reported that intestinal ILC2s contribute to T2DM and obesity in mice 60,61 . Here we demonstrate that DR3 agonistic treatment is an effective method for amelioration of T2DM regardless of the differences among various tissue resident ILC2s.…”

Section: Discussionmentioning

confidence: 99%

DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus

et al. 2020

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Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-κB pathways, and thus stimulates naïve and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM.

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Innate Lymphoid Cells in the Induction of Obesity

Cited by 75 publications

References 93 publications

RETRACTED: Living with Yourself: Innate Lymphoid Cell Immunometabolism

RETRACTED: Living with Yourself: Innate Lymphoid Cell Immunometabolism

Tumor-Derived Lactic Acid Contributes to the Paucity of Intratumoral ILC2s

DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus

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