Editors' ChoiceObesity

Innate lymphoid cells pack on the pounds

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Science Translational Medicine  17 Jul 2019:
Vol. 11, Issue 501, eaay3573
DOI: 10.1126/scitranslmed.aay3573


Small intestine innate lymphoid cells induce diet-related obesity in mouse models.

Innate lymphoid cells (ILCs) are a recently discovered group of lymphocytes that lack the rearranged antigen-specific receptors used by adaptive lymphocytes to recognize pathogens. Nevertheless, ILCs localize to tissues and rapidly respond through the production of cytokines to limit pathogen invasion. Broadly classified into three groups—ILC1s, ILC2s, and ILC3s—each ILC bears distinct functional, phenotypic, and transcriptional signatures. ILC1s produce antiviral cytokines and respond to tumors. ILC2s can promote allergic inflammation and limit helminth infection, whereas ILC3s protect epithelial surfaces, combating bacteria and fungi. In addition to the control of infection, data are accumulating regarding ILC function in many other biological processes.

Sasaki et al. examined the role of specific ILCs during diet-induced obesity, a global health problem with few nonsurgical interventions. Whereas mice that only lacked adaptive lymphocytes (Rag2–/–) gained weight after eating a high-fat diet for several weeks, mice with an additional absence of ILCs (Rag2–/– Il2rg–/–) failed to gain weight. Reconstitution of Rag2–/– Il2rg–/– mice with ILCs followed by a high-fat diet resulted in body weight increases, suggesting a direct role of these cells in inducing obesity. To determine which ILCs were contributing to weight gain, the authors depleted each subset using genetic approaches, finding that ablation of ILC2s prevented diet-induced obesity. ILC3s also contributed to weight gain, albeit to a lesser extent.

The authors next transferred either white adipose tissue ILC2s or small intestine (SI) ILC2s into Rag2–/– Il2rg–/– mice. Only mice receiving SI ILC2s experienced diet-associated obesity. Together, these experiments demonstrate a role for a specific ILC subset in weight gain due to a high-fat diet. Although the underlying mechanisms have not been determined, this study raises important questions regarding the function of these cells during infection and homeostasis. Because white adipose tissue is a reservoir for memory T cells that provide protection against pathogen challenge, ILC regulation of weight gain and adipose tissue stores could serve as another mechanism by which innate lymphocytes instruct adaptive immunity. On the other hand, the host-detrimental effects of obesity warrant further exploration of the possibility of modulating ILC2s to slow weight gain, even if this might dampen some adaptive immune responses.

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