2012
DOI: 10.1002/eji.201142018
|View full text |Cite
|
Sign up to set email alerts
|

Pulmonary innate lymphoid cells are major producers of IL‐5 and IL‐13 in murine models of allergic asthma

Abstract: Allergic asthma is characterized by chronic airway inflammation and hyperreactivity and is thought to be mediated by an adaptive T helper-2 (Th2) cell-type immune response. Here, we demonstrate that type 2 pulmonary innate lymphoid cells (ILC2s) significantly contribute to production of the key cytokines IL-5 and IL-13 in experimental asthma. In naive mice, lineage-marker negative ILC2s expressing IL-7Rα, CD25, Sca-1, and T1/ST2(IL-33R) were present in lungs and mediastinal lymph nodes (MedLNs) , IntroductionA… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

18
398
1
3

Year Published

2012
2012
2023
2023

Publication Types

Select...
7
1

Relationship

2
6

Authors

Journals

citations
Cited by 429 publications
(431 citation statements)
references
References 43 publications
(103 reference statements)
18
398
1
3
Order By: Relevance
“…In agreement with these findings, BAL fluids from HDM-challenged mice demonstrated increased levels of IL-33, as well as the type 2 cytokines IL-5 and IL-13 ( Figure 4B), which were associated with corresponding increases in lung tissue mRNA levels (Supplemental Figure 2B), and each of these responses was dramatically suppressed in HDM-treated Duox1 -/-mice. Serum levels of HDM-specific IgG1 and IgE indicated were highly similar between HDM-challenged wild-type and Duox1 -/-mice (Supplemental Figure 2C), suggesting that DUOX1-dependent type 2 responses are largely independent of adaptive immune responses and are most likely related to expansion and activation of ILC2s, which could serve as the primary source of IL-5, IL-3, and the EGFR ligand AREG in response to epithelial-derived cytokines, such as IL-33, within the lung (31)(32)(33). To address this, we generated single-cell suspensions of lung tissues from both control and HDM-challenged mice for in vitro restimulation with IL-33, which revealed dramatically enhanced production of IL-5, IL-13, and Areg by lung cell suspensions from HDM-challenged wild-type mice but not from Duox1 -/-mice ( Figure 4C).…”
Section: Resultsmentioning
confidence: 92%
See 1 more Smart Citation
“…In agreement with these findings, BAL fluids from HDM-challenged mice demonstrated increased levels of IL-33, as well as the type 2 cytokines IL-5 and IL-13 ( Figure 4B), which were associated with corresponding increases in lung tissue mRNA levels (Supplemental Figure 2B), and each of these responses was dramatically suppressed in HDM-treated Duox1 -/-mice. Serum levels of HDM-specific IgG1 and IgE indicated were highly similar between HDM-challenged wild-type and Duox1 -/-mice (Supplemental Figure 2C), suggesting that DUOX1-dependent type 2 responses are largely independent of adaptive immune responses and are most likely related to expansion and activation of ILC2s, which could serve as the primary source of IL-5, IL-3, and the EGFR ligand AREG in response to epithelial-derived cytokines, such as IL-33, within the lung (31)(32)(33). To address this, we generated single-cell suspensions of lung tissues from both control and HDM-challenged mice for in vitro restimulation with IL-33, which revealed dramatically enhanced production of IL-5, IL-13, and Areg by lung cell suspensions from HDM-challenged wild-type mice but not from Duox1 -/-mice ( Figure 4C).…”
Section: Resultsmentioning
confidence: 92%
“…Flow data were analyzed using FlowJo (Treestar). For flow sorting of ILC2s, mice were first subjected to 3 successive instillations of IL-33 (1 μg; Biolegend) over 5 days, as described previously (32). Lung single-cell suspensions were performed with the same antibodies described above, and < 2 × 10 5 ILC2s were sorted using the BD FACS Aria high-speed cell sorter and processed for total RNA isolation and RT-qPCR analysis (65).…”
Section: Methodsmentioning
confidence: 99%
“…In some experiments, a fraction of the isolated cells were stimulated with ionomycin (Sigma), PMA (Sigma), and GolgiPlug (BD Biosciences) at 37˚C for 4 h. Next, cells were stained for CD3, CD4, and intracellularly for IL-4, IL-5, IL-10, IL-13, IL-17, and IFN-g, after fixation with 2% PFA and permeabilization using a saponin-containing buffer (7,21 …”
Section: Flow Cytometric Analysismentioning
confidence: 99%
“…Because of their Th2 cytokine profile, they have been named group 2 ILCs (ILC2) and can be identified as lineage-negative cells expressing receptors for IL-2, IL-7, and IL-33 (4). The involvement of ILC2 in asthma was recently demonstrated in various mouse models, including HDM-driven allergic AAI (5)(6)(7)(8). ILC2 have also been identified in human lung and are associated with chronic rhinosinusitis (9)(10)(11).…”
mentioning
confidence: 99%
“…Activation of DCs occurs through the release of epithelial cytokines like thymic stromal lymphopoietin (TSLP), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-25, and the IL-1 family members IL-1a and IL-33 (Hammad et al, 2009;Kool et al, 2011;Phipps et al, 2009;Willart et al, 2012). Some of these lung-tissue-derived cytokines like IL-33 also induce cytokine production by ILC2s and tissue-resident memory Th2 cells (Coquet et al, 2015;Endo et al, 2015;Guo et al, 2015;Klein Wolterink et al, 2012).…”
Section: Introductionmentioning
confidence: 99%