IL-33–Responsive Lineage−CD25+CD44hi Lymphoid Cells Mediate Innate Type 2 Immunity and Allergic Inflammation in the Lungs

Bartemes, Kathleen R.; Izutsu, Koji; Kobayashi, Takao; Kephart, Gail M.; McKenzie, Andrew N. J.; Kita, Hirohito

doi:10.4049/jimmunol.1102832

Cited by 489 publications

(569 citation statements)

References 50 publications

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“…ILC2 are potently activated by the innate cytokines IL-33 and IL-25, and a vital role for these cells as a source of IL-13, required for the expulsion of intestinal helminths, has been determined (7,8,10). Furthermore, several groups reported an important role for ILC2 in allergy and airway inflammation and homeostasis (11)(12)(13)(14). We recently showed that transfer of ST2-expressing ILC2 into ST2-deficient mice was sufficient to mediate airway inflammation, mucus deposition, and cytokine production induced by administration of intranasal (i.n.)…”

mentioning

confidence: 99%

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Mirchandani

Besnard

Yip

et al. 2014

The Journal of Immunology

283

276

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CD4+ T cells have long been grouped into distinct helper subsets on the basis of their cytokine-secretion profile. In recent years, several subsets of innate lymphoid cell have been described as key producers of these same Th-associated cytokines. However, the functional relationship between Th cells and innate lymphoid cells (ILCs) remains unclear. We show in this study that lineage-negative ST2+ICOS+CD45+ type 2 ILCs and CD4+ T cells can potently stimulate each other’s function via distinct mechanisms. CD4+ T cell provision of IL-2 stimulates type 2 cytokine production by type 2 ILCs. By contrast, type 2 ILCs modulate naive T cell activation in a cell contact–dependent manner, favoring Th2 while suppressing Th1 differentiation. Furthermore, a proportion of type 2 ILCs express MHC class II and can present peptide Ag in vitro. Importantly, cotransfer experiments show that type 2 ILCs also can boost CD4+ T cell responses to Ag in vivo.

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mentioning

confidence: 99%

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Mirchandani

Besnard

Yip

et al. 2014

The Journal of Immunology

283

276

View full text Add to dashboard Cite

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“…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%

Enforced Expression of Gata3 in T Cells and Group 2 Innate Lymphoid Cells Increases Susceptibility to Allergic Airway Inflammation in Mice

KleinJan

Wolterink

Levani

et al. 2014

The Journal of Immunology

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Airway inflammation in allergic asthma reflects a threshold response of the innate immune system, including group 2 innate lymphoid cells (ILC2), followed by an adaptive Th2 cell–mediated response. Transcription factor Gata3 is essential for differentiation of both Th2 cells and ILC2. We investigated the effects of enforced Gata3 expression in T cells and ILC2 on the susceptibility of mice to allergic airway inflammation (AAI). We used CD2-Gata3 transgenic (Tg) mice with enforced Gata3 expression driven by the CD2 promoter, which is active both in T cells and during ILC2 development. CD2-Gata3 Tg mice and wild-type (WT) littermates were analyzed in mild models of AAI without adjuvants. Whereas OVA allergen exposure did not induce inflammation in WT controls, CD2-Gata3 Tg mice showed clear AAI and enhanced levels of IL-5 and IL-13 in bronchoalveolar lavage. Likewise, in house dust mite–driven asthma, CD2-Gata3 Tg mice were significantly more susceptible to AAI than WT littermates, whereby both ILC2 and Th2 cells were important cellular sources of IL-5 and IL-13 in bronchoalveolar lavage and lung tissue. Compared with WT littermates, CD2-Gata3 Tg mice contained increased numbers of ILC2, which expressed high levels of IL-33R and contributed significantly to early production of IL-4, IL-5, and IL-13. CD2-Gata3 Tg mice also had a unique population of IL-33–responsive non-B/non-T lymphoid cells expressing IFN-γ. Enforced Gata3 expression is therefore sufficient to enhance Th2 and ILC2 activity, and leads to increased susceptibility to AAI after mild exposure to inhaled harmless Ags that otherwise induce Ag tolerance.

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“…Although the cellular source of IL-17A in J H 2/2 mice during A. fumigatus infection remains unknown, recent studies suggest that macrophages or innate lymphoid cells might contribute to early IL-17 production in allergic asthma. 38,57,59,61 This observation highlights the need for further research to clarify the role of IL-17A in fungal asthma.…”

Section: Fungal Conidia Inhalation Significantly Increases Collagen Dmentioning

confidence: 98%

B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma

et al. 2014

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Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. J H 2/2 mice lack the JH gene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B lymphocytes in a number of immune responses; however, J H 2/2 mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and J H 2/2 mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of J H 2/2 mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the J H 2/2 animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exposure in the pulmonary compartment.

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IL-33–Responsive Lineage−CD25+CD44hi Lymphoid Cells Mediate Innate Type 2 Immunity and Allergic Inflammation in the Lungs

Cited by 489 publications

References 50 publications

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Enforced Expression of Gata3 in T Cells and Group 2 Innate Lymphoid Cells Increases Susceptibility to Allergic Airway Inflammation in Mice

B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma

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