An IL-9–pulmonary macrophage axis defines the allergic lung inflammatory environment

Fu, Yukui; Wang, Jocelyn; Zhou, Baohua; Pajulas, Abigail; Gao, Hongyu; Ramdas, Baskar; Koh, Byunghee; Ulrich, Bernd; Yang, Shuangshuang; Kapur, Reuben; Renauld, Jean‐Christophe; Paczesny, Sophie; Liu, Yunlong; Tighe, Robert; Licona-Limón, Paula; Flavell, Richard A.; Takatsuka, Shogo; Kitamura, Daisuke; Tepper, Robert S.; Sun, Jie; Kaplan, Mark H.

doi:10.1126/sciimmunol.abi9768

Cited by 33 publications

(34 citation statements)

References 66 publications

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“…Although mast cells are a known target of IL-9, in the recall model, we did not see a significant effect in this population on gene expression or cell number. In contrast, we did see changes in gene expression in interstitial macrophage populations that are a major IL-9–responsive population in a model of 6-week allergen exposure ( 71 ). We observed changes in gene expression in nonhematopoietic lung cells including mucin and other IL-13 target genes in airway epithelial cells.…”

Section: Discussionmentioning

confidence: 77%

Allergic airway recall responses require IL-9 from resident memory CD4 ⁺ T cells

et al. 2022

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Asthma is a chronic inflammatory lung disease with intermittent flares predominately mediated through memory T cells. Yet, the identity of long-term memory cells that mediate allergic recall responses is not well defined. In this report, using a mouse model of chronic allergen exposure followed by an allergen-free rest period, we characterized a subpopulation of CD4 + T cells that secreted IL-9 as an obligate effector cytokine. IL-9–secreting cells had a resident memory T cell phenotype, and blocking IL-9 during a recall challenge or deleting IL-9 from T cells significantly diminished airway inflammation and airway hyperreactivity. T cells secreted IL-9 in an allergen recall–specific manner, and secretion was amplified by IL-33. Using scRNA-seq and scATAC-seq, we defined the cellular identity of a distinct population of T cells with a proallergic cytokine pattern. Thus, in a recall model of allergic airway inflammation, IL-9 secretion from a multicytokine-producing CD4 + T cell population was required for an allergen recall response.

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Section: Discussionmentioning

confidence: 77%

Allergic airway recall responses require IL-9 from resident memory CD4 ⁺ T cells

et al. 2022

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“…Recent reports showed the presence of the CD11c + IM in OVA- and HDM-induced allergic inflammation 44 , 45 . Here we found that the induction of CD11c + IM is not limited to a Type 2 immune response, but also arose in the lung tumor environment where a qualitatively distinct immune response occurs.…”

Section: Discussionmentioning

confidence: 98%

Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9

Pajulas

Wang

et al. 2022

Nat Commun

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Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show that IL-9 signaling is associated with poor outcomes in patients with various forms of lung cancer, and is required for lung tumor growth in multiple mouse models. CD4+ T cell-derived IL-9 promotes the expansion of both CD11c+ and CD11c− interstitial macrophage populations in lung tumor models. Mechanistically, the IL-9/macrophage axis requires arginase 1 (Arg1) to mediate tumor growth. Indeed, adoptive transfer of Arg1+ but not Arg1- lung macrophages to Il9r−/− mice promotes tumor growth. Moreover, targeting IL-9 signaling using macrophage-specific nanoparticles restricts lung tumor growth in mice. Lastly, elevated expression of IL-9R and Arg1 in tumor lesions is associated with poor prognosis in lung cancer patients. Thus, our study suggests the IL-9/macrophage/Arg1 axis is a potential therapeutic target for lung cancer therapy.

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“…It would be interesting and informative to analyze more detailed immune cell phenotypes by flow cytometry in the future, particularly on lung macrophage and dendritic cells, with an up-to-date identification panel. [60] .…”

Section: Discussionmentioning

confidence: 99%

Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome

Yin

et al. 2022

Biomedicine & Pharmacotherapy

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An IL-9–pulmonary macrophage axis defines the allergic lung inflammatory environment

Cited by 33 publications

References 66 publications

Allergic airway recall responses require IL-9 from resident memory CD4 ⁺ T cells

Allergic airway recall responses require IL-9 from resident memory CD4 ⁺ T cells

Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9

Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome

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An IL-9–pulmonary macrophage axis defines the allergic lung inflammatory environment

Cited by 33 publications

References 66 publications

Allergic airway recall responses require IL-9 from resident memory CD4 + T cells

Allergic airway recall responses require IL-9 from resident memory CD4 + T cells

Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9

Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome

Contact Info

Product

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About

Allergic airway recall responses require IL-9 from resident memory CD4 ⁺ T cells

Allergic airway recall responses require IL-9 from resident memory CD4 ⁺ T cells