Basophils Are Important for Development of Allergic Skin Inflammation

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2024 Feb 9

PMID 38336257

Authors

Juan-Manuel Leyva-Castillo

Daniela Vega-Mendoza

Maria Strakosha

Liwen Deng

Samantha Choi

Kensuke Miyake

Hajime Karasuyama

Isaac M Chiu

Wanda Phipatanakul

Raif S Geha

Affiliations

Soon will be listed here.

Abstract

Background: Atopic dermatitis skin lesions exhibit increased infiltration by basophils. Basophils produce IL-4, which plays an important role in the pathogenesis of atopic dermatitis.

Objective: We sought to determine the role of basophils in a mouse model of antigen-driven allergic skin inflammation.

Methods: Wild-type mice, mice with selective and inducible depletion of basophils, and mice expressing Il4-driven enhanced green fluorescent protein were subjected to epicutaneous sensitization with ovalbumin or saline. Sensitized skin was examined by histology for epidermal thickening. Cells were analyzed for surface markers and intracellular expression of enhanced green fluorescent protein by flow cytometry. Gene expression was evaluated by real-time reverse transcription-quantitative PCR.

Results: Basophils were important for epidermal hyperplasia, dermal infiltration by CD4 T cells, mast cells, and eosinophils in ovalbumin-sensitized mouse skin and for the local and systemic T2 response to epicutaneous sensitization. Moreover, basophils were the major source of IL-4 in epicutaneous-sensitized mouse skin and promote the ability of dendritic cells to drive T2 polarization of naive T cells.

Conclusion: Basophils play an important role in the development of allergic skin inflammation induced by cutaneous exposure to antigen in mice.

Citing Articles

Difamilast, a Topical Phosphodiesterase 4 Inhibitor, Produces Soluble ST2 via the AHR-NRF2 Axis in Human Keratinocytes.

Tsuji G, Yumine A, Kawamura K, Takemura M, Kido-Nakahara M, Yamamura K Int J Mol Sci. 2024; 25(14).

PMID: 39063153 PMC: 11277015. DOI: 10.3390/ijms25147910.

IL-4 acts on skin-derived dendritic cells to promote the T2 response to cutaneous sensitization and the development of allergic skin inflammation.

Leyva-Castillo J, Das M, Strakosha M, McGurk A, Artru E, Kam C J Allergy Clin Immunol. 2024; 154(6):1462-1471.e3.

PMID: 38996877 PMC: 11625010. DOI: 10.1016/j.jaci.2024.06.021.

BASOPHILS ACTIVATE PRURICEPTOR-LIKE VAGAL SENSORY NEURONS.

Wang J, Nikpoor A, Crosson T, Kaufmann E, Rafei M, Talbot S bioRxiv. 2024; .

PMID: 38915548 PMC: 11195257. DOI: 10.1101/2024.06.11.598517.

Atopic dermatitis and food allergy: More than sensitization.

Davis K, Claudio-Etienne E, Frischmeyer-Guerrerio P Mucosal Immunol. 2024; 17(5):1128-1140.

PMID: 38906220 PMC: 11471387. DOI: 10.1016/j.mucimm.2024.06.005.

References

Yosipovitch G, Rosen J, Hashimoto T . Itch: From mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018; 142(5):1375-1390. DOI: 10.1016/j.jaci.2018.09.005. View

Karasuyama H, Miyake K, Yoshikawa S, Yamanishi Y . Multifaceted roles of basophils in health and disease. J Allergy Clin Immunol. 2017; 142(2):370-380. DOI: 10.1016/j.jaci.2017.10.042. View

Gessner A, Mohrs K, Mohrs M . Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production. J Immunol. 2005; 174(2):1063-72. DOI: 10.4049/jimmunol.174.2.1063. View

Hammad H, Plantinga M, Deswarte K, Pouliot P, Willart M, Kool M . Inflammatory dendritic cells--not basophils--are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. J Exp Med. 2010; 207(10):2097-111. PMC: 2947072. DOI: 10.1084/jem.20101563. View

Hashimoto T, Rosen J, Sanders K, Yosipovitch G . Possible roles of basophils in chronic itch. Exp Dermatol. 2018; 28(12):1373-1379. DOI: 10.1111/exd.13705. View

Kojima T, Obata K, Mukai K, Sato S, Takai T, Minegishi Y . Mast cells and basophils are selectively activated in vitro and in vivo through CD200R3 in an IgE-independent manner. J Immunol. 2007; 179(10):7093-100. DOI: 10.4049/jimmunol.179.10.7093. View

Tang H, Cao W, Kasturi S, Ravindran R, Nakaya H, Kundu K . The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol. 2010; 11(7):608-17. PMC: 3145206. DOI: 10.1038/ni.1883. View

Leisten S, Oyoshi M, Galand C, Hornick J, Gurish M, Geha R . Development of skin lesions in filaggrin-deficient mice is dependent on adaptive immunity. J Allergy Clin Immunol. 2013; 131(4):1247-50, 1250.e1. DOI: 10.1016/j.jaci.2012.12.1576. View

Omori-Miyake M, Yamashita M, Tsunemi Y, Kawashima M, Yagi J . In vitro assessment of IL-4- or IL-13-mediated changes in the structural components of keratinocytes in mice and humans. J Invest Dermatol. 2013; 134(5):1342-1350. DOI: 10.1038/jid.2013.503. View

10.

Sokol C, Barton G, Farr A, Medzhitov R . A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol. 2008; 9(3):310-8. PMC: 3888112. DOI: 10.1038/ni1558. View

11.

Obata K, Mukai K, Tsujimura Y, Ishiwata K, Kawano Y, Minegishi Y . Basophils are essential initiators of a novel type of chronic allergic inflammation. Blood. 2007; 110(3):913-20. DOI: 10.1182/blood-2007-01-068718. View

12.

Mohrs K, Wakil A, Killeen N, Locksley R, Mohrs M . A two-step process for cytokine production revealed by IL-4 dual-reporter mice. Immunity. 2005; 23(4):419-29. PMC: 2826320. DOI: 10.1016/j.immuni.2005.09.006. View

13.

Yoon J, Leyva-Castillo J, Wang G, Galand C, Oyoshi M, Kumar L . IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med. 2016; 213(10):2147-66. PMC: 5032726. DOI: 10.1084/jem.20150376. View

14.

Otsuka A, Nakajima S, Kubo M, Egawa G, Honda T, Kitoh A . Basophils are required for the induction of Th2 immunity to haptens and peptide antigens. Nat Commun. 2013; 4:1739. PMC: 3644090. DOI: 10.1038/ncomms2740. View

15.

Pellefigues C, Naidoo K, Mehta P, Schmidt A, Jagot F, Roussel E . Basophils promote barrier dysfunction and resolution in the atopic skin. J Allergy Clin Immunol. 2021; 148(3):799-812.e10. PMC: 8410897. DOI: 10.1016/j.jaci.2021.02.018. View

16.

Kim D, Kobayashi T, Nagao K . Research Techniques Made Simple: Mouse Models of Atopic Dermatitis. J Invest Dermatol. 2019; 139(5):984-990.e1. PMC: 6555635. DOI: 10.1016/j.jid.2019.02.014. View

17.

Oyoshi M, He R, Kumar L, Yoon J, Geha R . Cellular and molecular mechanisms in atopic dermatitis. Adv Immunol. 2009; 102:135-226. DOI: 10.1016/S0065-2776(09)01203-6. View

18.

Nagashima N, Ugajin T, Miyake K, Walls A, Namiki T, Yokozeki H . Cutaneous basophil infiltration in atopic dermatitis is associated with abundant epidermal infiltration of helper T cells: A preliminary retrospective study. J Dermatol. 2023; 51(1):130-134. DOI: 10.1111/1346-8138.16987. View

19.

Ohnmacht C, Schwartz C, Panzer M, Schiedewitz I, Naumann R, Voehringer D . Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths. Immunity. 2010; 33(3):364-74. DOI: 10.1016/j.immuni.2010.08.011. View

20.

Takahashi K, Miyake K, Ito J, Shimamura H, Suenaga T, Karasuyama H . Topical Application of a PDE4 Inhibitor Ameliorates Atopic Dermatitis through Inhibition of Basophil IL-4 Production. J Invest Dermatol. 2023; 144(5):1048-1057.e8. DOI: 10.1016/j.jid.2023.09.272. View