title: Airway epithelial cells modify immune responses by inducing an anti-inflammatory microenvironment.
abstract: The upper airways are prone to contact with pathogenic as well as non-pathogenic microbes, therefore immune recognition principles have to be tightly controlled. Here we show that human BEAS-2B bronchial epithelial cells inhibited secretion of the pro-inflammatory cytokines TNF-alpha and IL-12 by monocytes, macrophages and dendritic cells. This inhibitory effect could be transferred by supernatant of resting BEAS-2B cells and was also observed when primary murine tracheal epithelial cells were prepared. In contrast to inhibition of pro-inflammatory cytokine secretion epithelial cell-conditioned dendritic cells showed increased expression of IL-10 and arginase-1, thus displaying properties of alternative activation. Accordingly, Toll-like receptor-mediated up-regulation of CD40, CD86 and PD-L2 (CD273) on murine dendritic cells was reduced in the presence of bronchial epithelial cell supernatant. However, expression of negative regulatory PD-L1 (CD274) was increased and dendritic cell induced proliferation of T lymphocytes was diminished. Epithelial cells also showed a direct inhibitory effect on T lymphocyte proliferation and this was due to the constitutive secretion of TGF-beta by bronchial epithelial cells. Moreover, epithelial cell-conditioned T lymphocytes showed increased differentiation towards IL-10-producing Tr1 cells. The results indicate that bronchial epithelial cells induce a non-inflammatory microenvironment that regulates local immune homeostasis.
authors.affiliation: Department of Hygiene and Medical Microbiology, University Heidelberg, Heidelberg, Germany.
authors.forename: Anja K
authors.initials: AK
authors.lastname: Mayer
authors.forename: Holger
authors.initials: H
authors.lastname: Bartz
authors.forename: Fabian
authors.initials: F
authors.lastname: Fey
authors.forename: Lotte M
authors.initials: LM
authors.lastname: Schmidt
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Dalpke
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001119:Arginase / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D017077:Culture Media, Conditioned; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001119:Arginase