Interleukin-9 Promotes Mast Cell Progenitor Proliferation and CCR2-dependent Mast Cell Migration in Allergic Airway Inflammation

Overview

Journal Mucosal Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2023 May 12

PMID 37172907

Authors

Abigail Pajulas

Yongyao Fu

Cherry C L Cheung

Michelle Chu

Anthony Cannon

Nada Alakhras

Jilu Zhang

Benjamin J Ulrich

Andrew S Nelson

Baohua Zhou

Mark H Kaplan

Affiliations

Soon will be listed here.

Abstract

Allergic asthma is a chronic lung disease characterized by airway hyperresponsiveness and cellular infiltration that is exacerbated by immunoglobulin E-dependent mast cell (MC) activation. Interleukin-9 (IL-9) promotes MC expansion during allergic inflammation but precisely how IL-9 expands tissue MCs and promotes MC function is unclear. In this report, using multiple models of allergic airway inflammation, we show that both mature MCs (mMCs) and MC progenitors (MCp) express IL-9R and respond to IL-9 during allergic inflammation. IL-9 acts on MCp in the bone marrow and lungs to enhance proliferative capacity. Furthermore, IL-9 in the lung stimulates the mobilization of CCR2+ mMC from the bone marrow and recruitment to the allergic lung. Mixed bone marrow chimeras demonstrate that these are intrinsic effects in the MCp and mMC populations. IL-9-producing T cells are both necessary and sufficient to increase MC numbers in the lung in the context of allergic inflammation. Importantly, T cell IL-9-mediated MC expansion is required for the development of antigen-induced and MC-dependent airway hyperreactivity. Collectively, these data demonstrate that T cell IL-9 induces lung MC expansion and migration by direct effects on the proliferation of MCp and the migration of mMC to mediate airway hyperreactivity.

Citing Articles

Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial.

Xu G, Paglialunga S, Qian X, Ding R, Webster K, van Haarst A Front Immunol. 2024; 15():1495540.

PMID: 39717777 PMC: 11663749. DOI: 10.3389/fimmu.2024.1495540.

Toll-like receptor activation induces airway obstruction and hyperresponsiveness in guinea pigs.

Xiang Y, Liu J, Nie M, Nilsson G, Safholm J, Adner M Respir Res. 2024; 25(1):421.

PMID: 39614276 PMC: 11607803. DOI: 10.1186/s12931-024-03050-3.

Regulation of Airway Epithelial-Derived Alarmins in Asthma: Perspectives for Therapeutic Targets.

Hansi R, Ranjbar M, Whetstone C, Gauvreau G Biomedicines. 2024; 12(10).

PMID: 39457624 PMC: 11505104. DOI: 10.3390/biomedicines12102312.

Immunologic aspects of asthma: from molecular mechanisms to disease pathophysiology and clinical translation.

Xie C, Yang J, Gul A, Li Y, Zhang R, Yalikun M Front Immunol. 2024; 15:1478624.

PMID: 39439788 PMC: 11494396. DOI: 10.3389/fimmu.2024.1478624.

Functional diversity and regulation of IL-9-producing T cells in cancer immunotherapy.

Kalim M, Jing R, Guo W, Xing H, Lu Y Cancer Lett. 2024; 606:217306.

PMID: 39426662 PMC: 11675864. DOI: 10.1016/j.canlet.2024.217306.

References

Jones T, Hallgren J, Humbles A, Burwell T, Finkelman F, Alcaide P . Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells. J Immunol. 2009; 183(8):5251-60. PMC: 2782612. DOI: 10.4049/jimmunol.0901471. View

Liu A, Dwyer D, Jones T, Bankova L, Shen S, Katz H . Mast cells recruited to mesenteric lymph nodes during helminth infection remain hypogranular and produce IL-4 and IL-6. J Immunol. 2013; 190(4):1758-66. PMC: 3563837. DOI: 10.4049/jimmunol.1202567. View

Nouri-Aria K, Pilette C, Jacobson M, Watanabe H, Durham S . IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen exposure: effect of immunotherapy. J Allergy Clin Immunol. 2005; 116(1):73-9. DOI: 10.1016/j.jaci.2005.03.011. View

Carroll N, Mutavdzic S, James A . Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J. 2002; 19(5):879-85. DOI: 10.1183/09031936.02.00275802. View

Grunig G, Warnock M, Wakil A, Venkayya R, Brombacher F, Rennick D . Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998; 282(5397):2261-3. PMC: 3897229. DOI: 10.1126/science.282.5397.2261. View

White B, Leon F, White W, Robbie G . Two first-in-human, open-label, phase I dose-escalation safety trials of MEDI-528, a monoclonal antibody against interleukin-9, in healthy adult volunteers. Clin Ther. 2009; 31(4):728-40. DOI: 10.1016/j.clinthera.2009.04.019. View

Renauld J, Kermouni A, Vink A, Louahed J, Van Snick J . Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis. J Leukoc Biol. 1995; 57(3):353-60. DOI: 10.1002/jlb.57.3.353. View

Forbes E, Groschwitz K, Abonia J, Brandt E, Cohen E, Blanchard C . IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med. 2008; 205(4):897-913. PMC: 2292227. DOI: 10.1084/jem.20071046. View

Chen C, Grimbaldeston M, Tsai M, Weissman I, Galli S . Identification of mast cell progenitors in adult mice. Proc Natl Acad Sci U S A. 2005; 102(32):11408-13. PMC: 1183570. DOI: 10.1073/pnas.0504197102. View

10.

Knoops L, Louahed J, Van Snick J, Renauld J . IL-9 promotes but is not necessary for systemic anaphylaxis. J Immunol. 2005; 175(1):335-41. DOI: 10.4049/jimmunol.175.1.335. View

11.

Hallgren J, Gurish M . Mast cell progenitor trafficking and maturation. Adv Exp Med Biol. 2011; 716:14-28. PMC: 3554263. DOI: 10.1007/978-1-4419-9533-9_2. View

12.

Dahlin J, Ding Z, Hallgren J . Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice. Stem Cells Dev. 2015; 24(14):1703-11. PMC: 4499794. DOI: 10.1089/scd.2014.0553. View

13.

Alakhras N, Shin J, Smith S, Sinn A, Zhang W, Hwang G . Peanut allergen inhibition prevents anaphylaxis in a humanized mouse model. Sci Transl Med. 2023; 15(682):eadd6373. PMC: 10205092. DOI: 10.1126/scitranslmed.add6373. View

14.

Bankova L, Dwyer D, Liu A, Austen K, Gurish M . Maturation of mast cell progenitors to mucosal mast cells during allergic pulmonary inflammation in mice. Mucosal Immunol. 2014; 8(3):596-606. PMC: 4390399. DOI: 10.1038/mi.2014.91. View

15.

Mendez-Enriquez E, Hallgren J . Mast Cells and Their Progenitors in Allergic Asthma. Front Immunol. 2019; 10:821. PMC: 6548814. DOI: 10.3389/fimmu.2019.00821. View

16.

TOWNSEND J, Fallon G, Matthews J, Smith P, Jolin E, McKenzie N . IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity. 2000; 13(4):573-83. DOI: 10.1016/s1074-7613(00)00056-x. View

17.

Fu Y, Wang J, Zhou B, Pajulas A, Gao H, Ramdas B . An IL-9-pulmonary macrophage axis defines the allergic lung inflammatory environment. Sci Immunol. 2022; 7(68):eabi9768. PMC: 8991419. DOI: 10.1126/sciimmunol.abi9768. View

18.

Wan J, Huang L, Ji X, Yao S, Abdelaziz M, Cai W . HMGB1-induced ILC2s activate dendritic cells by producing IL-9 in asthmatic mouse model. Cell Immunol. 2020; 352:104085. DOI: 10.1016/j.cellimm.2020.104085. View

19.

Tomar S, Ganesan V, Sharma A, Zeng C, Waggoner L, Smith A . IL-4-BATF signaling directly modulates IL-9 producing mucosal mast cell (MMC9) function in experimental food allergy. J Allergy Clin Immunol. 2020; 147(1):280-295. PMC: 7856198. DOI: 10.1016/j.jaci.2020.08.043. View

20.

Moretti S, Renga G, Oikonomou V, Galosi C, Pariano M, Iannitti R . A mast cell-ILC2-Th9 pathway promotes lung inflammation in cystic fibrosis. Nat Commun. 2017; 8:14017. PMC: 5241810. DOI: 10.1038/ncomms14017. View