title: Airway epithelial cells condition dendritic cells to express multiple immune surveillance genes.
abstract: Increasing evidence suggests that crosstalk between airway epithelial cells (AEC) and adjacent dendritic cells (DC) tightly regulates airway mucosal DC function in steady state. AEC are known to express multiple immuno-modulatory factors, though detailed information on how this influences human DC function remains incomplete. We recently demonstrated using an in vitro coculture model that AEC alter differentiation of monocytes into DC in a manner that inhibits expression of potentially damaging Th2 effector function. In the current study, we have extended these findings to examine other aspects of DC function. Using micro-array technology we show that multiple genes important for immune surveillance are significantly over expressed in purified AEC-conditioned DC, compared to control DC. These findings were confirmed by quantitative real time PCR or flow cytometry in an independent sample set. In particular, AEC-conditioned DC showed selective upregulation of chemokines that recruit Th1 cells, but minimal change in chemokines linked to Th2 cell recruitment. AEC-conditioned DC were also characterized by enhanced expression of complement family genes (C1QB, C2, CD59 and SERPING1), Fcγ receptor genes (FCGR1A, FCGR2A, FCGR2B and FCGR2C), signaling lymphocytic activation molecule family member 1 (SLAM), programmed death ligands 1 and 2, CD54 and CD200R1, relative to control DC. These findings suggest that AEC conditioning facilitates the capacity of DC to react to danger signals, to enhance leukocyte recruitment, especially of Th1 effector cells, and to interact with other immune cell populations while minimizing the risks of excessive inflammation leading to tissue damage.
authors.affiliation: Telethon Institute for Child Health Research, and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Rate
authors.forename: Anthony
authors.initials: A
authors.lastname: Bosco
authors.forename: Kathy L
authors.initials: KL
authors.lastname: McKenna
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
mesh_terms: D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007249:Inflammation; D007370:Interferon Type I / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology; D013997:Time Factors
chemical_list: D018925:Chemokines; D007370:Interferon Type I; D017452:Receptors, IgG