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Macrophages are critical to the maintenance of IL-13-dependent lung inflammation and fibrosis

Lookup NU author(s): Dr Lee BorthwickORCiD, Professor Andrew FisherORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

Abstract

The roles of macrophages in type 2-driven inflammation and fibrosis remain unclear. Here, using CD11b-diphtheria toxin receptor (DTR) transgenic mice and three models of interleukin 13 (IL-13)-dependent inflammation, fibrosis, and immunity, we show that CD11b(+) F4/80(+) Ly6C(+) macrophages are required for the maintenance of type 2 immunity within affected tissues but not secondary lymphoid organs. Direct depletion of macrophages during the maintenance or resolution phases of secondary Schistosoma mansoni egg-induced granuloma formation caused a profound decrease in inflammation, fibrosis, and type 2 gene expression. Additional studies with CD11c-DTR and CD11b/CD11c-DTR double-transgenic mice suggested that macrophages but not dendritic cells were critical. Mechanistically, macrophage depletion impaired effector CD4(+) T helper type 2 (Th2) cell homing and activation within the inflamed lung. Depletion of CD11b(+) F4/80(+) Ly6C(+) macrophages similarly reduced house dust mite-induced allergic lung inflammation and suppressed IL-13-dependent immunity to the nematode parasite Nippostrongylus brasiliensis. Consequently, therapeutic strategies targeting macrophages offer a novel approach to ameliorate established type 2 inflammatory diseases.

Publication metadata

Author(s): Borthwick LA, Barron L, Hart KM, Vannella KM, Thompson RW, Oland S, Cheever A, Sciurba J, Ramalingam TR, Fisher AJ, Wynn TA

Publication type: Article

Publication status: Published

Journal: Mucosal Immunology

Year: 2016

Volume: 9

Issue: 1

Pages: 38-55

Print publication date: 01/01/2016

Online publication date: 29/04/2015

Acceptance date: 07/03/2015

Date deposited: 23/05/2016

ISSN (print): 1933-0219

ISSN (electronic): 1935-3456

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/mi.2015.34

DOI: 10.1038/mi.2015.34

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