Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

Monticelli, Laurel A.; Buck, Michael D.; Flamar, Anne-Laure; Saenz, Steven A.; Wojno, Elia D. Tait; Yudanin, Naomi; Osborne, Lisa C.; Hepworth, Matthew R.; Tran, Sara V.; Rodewald, Hans Reimer; Shah, Hardik; Cross, Justin R.; Diamond, Joshua M.; Cantu, Edward; Christie, Jason D.; Pearce, Erika L.; Artis, David

doi:10.1038/ni.3421

Cited by 241 publications

(267 citation statements)

References 49 publications

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“…Studies of lung regeneration after partial pneumonectomy support the concept that interactions among activated macrophages and lung parenchymal cells create a proliferative microenvironment (22). In the present study, regeneration was associated with marked increase in inflammatory cell expression of ARG1 and other markers of atypical macrophage activation (M2-like), including RETNLA and CD206, proposed to contribute to repair processes (22,41,42). Alveolar macrophages expressing CD206 and ARG1 were identified by immunofluorescence confocal microscopy in both Abca3-cKO mouse lung during regeneration and in lung tissue from patients with severe lung disease caused by ABCA3 mutations.…”

Section: Discussionsupporting

confidence: 71%

Alveolar injury and regeneration following deletion of ABCA3

Rindler¹,

Stockman²,

Filuta³

et al. 2017

JCI Insight

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Section: Discussionsupporting

confidence: 71%

Alveolar injury and regeneration following deletion of ABCA3

Rindler¹,

Stockman²,

Filuta³

et al. 2017

JCI Insight

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“…IL-25 and IL-33 both upregulated genes associated with ILC2 activation, including Il5 , Klrg1 , and Arg1 , while other genes, such as Areg , were preferentially induced by one alarmin but not the other (Extended Data Fig. 1i) 2,16 .…”

Section: Alarmins Induce Heterogeneity In Ilc2smentioning

confidence: 99%

The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation

Wallrapp

Riesenfeld

Burkett

et al. 2017

Nature

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524

480

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Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes. The neuropeptide receptor Nmur1 was preferentially expressed by ILC2s at steady state and after IL-25 stimulation. Neuromedin U (NMU), the ligand of NMUR1, activated ILC2s in vitro, and in vivo co-administration of NMU with IL-25 strongly amplified allergic inflammation. Loss of NMU–NMUR1 signalling reduced ILC2 frequency and effector function, and altered transcriptional programs following allergen challenge in vivo. Thus, NMUR1 signalling promotes inflammatory ILC2 responses, highlighting the importance of neuro-immune crosstalk in allergic inflammation at mucosal surfaces.

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“…Myeloid cell Arg1 has immunosuppressive capacities (Rodriguez et al 2004;Munder et al 2006), and, recently, Arg1 was shown to perform a cell-intrinsic role in the regulation of ILC2 metabolism and type 2 inflammation in the lung (Monticelli et al 2016).…”

Section: Metabolites As Regulators Of Symbiosismentioning

confidence: 99%

Metabolites: messengers between the microbiota and the immune system

2016

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The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases.The mammalian intestine harbors a dense and complex microbial community, termed the microbiota. The commensal microbiome and, in particular, the dense and diverse microbial community inhabiting the gastrointestinal tract play a pivotal role in the maintenance of organismal homeostasis and stable physiology. Research over the last decade has highlighted the concept that the eukaryotic host and its microbiota, rather than existing in isolation, compose a complex meta-organism termed the "holobiont," jointly regulating multiple aspects of mammalian physiology, including immune system development, metabolism, and nervous system function (Sommer and Backhed 2013). The interaction between the microbiota and the host is most prominent at mucosal surfaces, which provide an interface between the mostly microbe-free host, the microbiota, and the environment. At the same time, the presence of the microbial community within the eukaryotic host necessitates the development of a sophisticated immune system that controls and maintains a beneficial symbiosis of the holobiont through the continuous communication between the microbiome and the host.

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Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

Cited by 241 publications

References 49 publications

Alveolar injury and regeneration following deletion of ABCA3

Alveolar injury and regeneration following deletion of ABCA3

The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation

Metabolites: messengers between the microbiota and the immune system

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