title: Induction of a homeostatic circuit in lung tissue by microbial compounds.
abstract: TGFbeta presented and activated by integrin alphavbeta6 expressed on alveolar epithelial cells (AEC) continuously inhibits the functionality of alveolar macrophages (AM). Despite this inhibition, AM retain their ability to respond to inhaled microorganisms. Herein we describe a homeostatic circuit through which the effects of microbial products on macrophages transiently circumvent this inhibition by repressing alphavbeta6 expression on AEC. Subsequent production of matrix metalloproteinases by activated AM activates latent TGFbeta, reinduces alphavbeta6 expression, and thereby reinstates tonic inhibition of AM function. Our results reveal how AM can be activated while minimizing their potential to inflict collateral damage to the adjacent lung tissue and indicate that tissue-specific microenvironmental factors shape organ-specific defense strategies against microbial invasion.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, 92093, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takabayshi
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Redecke
authors.forename: Lucinda
authors.initials: L
authors.lastname: Beck
authors.forename: Donald
authors.initials: D
authors.lastname: Guiney
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
authors.forename: Eyal
authors.initials: E
authors.lastname: Raz
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology*; D015153:Blotting, Western; D002450:Cell Communication / Q000276:immunology*; D005260:Female; D006706:Homeostasis / Q000276:immunology*; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology*; D020782:Matrix Metalloproteinases / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020239:Receptor Cross-Talk / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; C073878:integrin alphavbeta6; D020782:Matrix Metalloproteinases