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Type 2 innate lymphoid cells constitutively express arginase-I in the naive and inflamed lung.

ABSTRACT: Arg1 is produced by AAMs and is proposed to have a regulatory role during asthma and allergic inflammation. Here, we use an Arg1 reporter mouse to identify additional cellular sources of the enzyme in the lung. We demonstrate that ILC2s express Arg1 at rest and during infection with the migratory helminth Nippostrongylus brasiliensis. In contrast to AAMs, which express Arg1 following IL-4/IL-13-mediated STAT6 activation, ILC2s constitutively express the enzyme in a STAT6-independent manner. Although ILC2s deficient in the IL-33R subunit T1/ST2 maintain Arg1 expression, IL-33 can regulate total lung Arg1 by expanding the ILC2 population and by activating macrophages indirectly via STAT6. Finally, we find that ILC2 Arg1 does not mediate ILC2 accumulation, ILC2 production of IL-5 and IL-13, or collagen production during N. brasiliensis infection. Thus, ILC2s are a novel source of Arg1 in resting tissue and during allergic inflammation.

SUBMITTER: Bando JK

PROVIDER: S-EPMC3800063 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Group 2 Innate Lymphoid Cells Express Functional NKp30 Receptor Inducing Type 2 Cytokine Production.

Project description:Group 2 innate lymphoid cells (ILC2) are important in effector functions for eliciting allergic inflammation, parasite defense, epithelial repair, and lipid homeostasis. ILC2 lack rearranged Ag-specific receptors, and although many soluble factors such as cytokines and lipid mediators can influence ILC2, direct interaction of these cells with the microenvironment and other cells has been less explored. Natural cytotoxicity receptors are expressed by subsets of group 1 ILC and group 3 ILC and thought to be important for their effector function, but they have not been shown to be expressed by ILC2. Therefore, we sought to investigate the expression and functional properties of the natural cytotoxicity receptor NKp30 on human ILC2. A subset of ex vivo and cultured ILC2 express NKp30 that upon interaction with its cognate activatory ligand B7-H6 induces rapid production of type 2 cytokines. This interaction can be blocked by NKp30 blocking Ab and an inhibitory ligand, galectin-3. Higher expression of B7-H6 was observed in lesional skin biopsies of patients with atopic dermatitis, and incubation of keratinocytes with proinflammatory and type 2 cytokines upregulated B7-H6, leading to increased ILC2 cytokine production. NKp30-B7-H6 interaction is a novel cell contact mechanism that mediates activation of ILC2 and identifies a potential target for the development of novel therapeutics for atopic dermatitis and other atopic diseases.

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CD90 is not constitutively expressed in functional innate lymphoid cells.

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The prostaglandin D₂ receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung.

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

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| S-EPMC4170007 | biostudies-literature

Allergen challenge in allergic rhinitis rapidly induces increased peripheral blood type 2 innate lymphoid cells that express CD84.

Project description: Not available

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Lung type 3 innate lymphoid cells respond early following <i>Mycobacterium tuberculosis</i> infection.

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| S-EPMC11005430 | biostudies-literature

Type 2 innate lymphoid cells control eosinophil homeostasis.

Project description:Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80?years ago, and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins mediate eosinophil development and survival, and tissue recruitment, respectively, the processes underlying the basal regulation of these signals remain unknown. Here we show that serum IL-5 levels are maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 cells secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive, ILC2 cells co-express IL-5 and IL-13; this co-expression is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide also stimulates ILC2 cells through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 cells regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.

| S-EPMC3795960 | biostudies-other

Soluble ST2 suppresses the effect of interleukin-33 on lung type 2 innate lymphoid cells.

Project description:Type 2 innate lymphoid cells (ILC2) in lungs produce interleukin (IL)-5 and IL-13 in response to IL-33 and may contribute to the development of allergic diseases such as asthma. However, little is known about negative regulators and effective inhibitors controlling ILC2 function. Here, we show that soluble ST2, a member of the IL-1 receptor family, suppresses the effect of IL-33 on lung ILC2 in vitro. Stimulation with IL-33 to naïve ILC2 induced morphological change and promoted cell proliferation. In addition, IL-33 upregulated expression of cell surface molecules including IL-33 receptor and induced production of IL-5 and IL-13, but not IL-4. Pretreatment with soluble ST2 suppressed IL-33-mediated responses of ILC2. The results suggest that soluble ST2 acts as a decoy receptor for IL-33 and protects ILC2 from IL-33 stimulation.

| S-EPMC5600343 | biostudies-literature

CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines.

Project description:BackgroundRecent studies show that innate lymphoid cells (ILCs) contribute to the development of chronic inflammation and autoimmune disease. In this study, we assessed the ILC function in the development of rheumatoid arthritis (RA).MethodsIn a mouse model of collagen-induced arthritis (CIA), we identified and purified the ILC subsets in peripheral blood (PB), local lymph nodes (LNs), and joints by fluorescence-activated cell sorting and used quantitative PCR to assess the expression levels of representative cytokines. We also correlated the frequencies of each ILC subset in synovial fluid (SF) with clinical parameters in RA patients.ResultsIn the CIA model, the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p = 0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p = 0.015). In RA patients, the proportion of CCR6+ ILCs in SF was positively correlated with tender joint counts (TJC) and swollen joint counts (SJC) (ρ=0.689, p = 0.0032 and ρ=0.644, p = 0.0071, respectively). Levels of CC chemokine ligand 20 (CCL20) increased in SF of patients with RA and were significantly correlated with CCR6+ ILC number (ρ=0.697, p = 0.0001).ConclusionCCR6+ ILC3s may play some roles in the development of RA through the production of IL-17 and IL-22.

| S-EPMC6716915 | biostudies-literature

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