PMID- 28470729 OWN - NLM STAT- MEDLINE DCOM- 20171016 LR - 20181113 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 189 IP - 3 DP - 2017 Sep TI - Airway epithelial cells enhance the immunogenicity of human myeloid dendritic cells under steady state. PG - 279-289 LID - 10.1111/cei.12983 [doi] AB - Dendritic cells (DCs) and airway epithelial cells (AECs) are in close proximity, and AECs secrete factors such as retinoic acid which induce tolerance in DCs at homeostasis. However, the question remains as to how DCs in the lung are able to respond to pathogens in the immunosuppressive environment. Using an in vitro human myeloid DC (mDC)-AEC co-culture system, we demonstrate that AECs induced several gene changes in the mDCs cultured with AECs compared to the mDCs not cultured with AECs. Analysis revealed that several chemokine genes were altered. These chemokine genes could serve to attract neutrophils, natural killer (NK) T as well as T helper type 1 (Th1)/Th2 cells to the airways. Genes priming lipid and major histocompatibility complex (MHC) class II antigen presentation were also up-regulated, along with certain anti-microbial protein genes. In addition, the expression and function of pathogen-sensing Toll-like receptors (TLRs) as well as Nod-like receptors (NLRs) and their downstream signalling molecules were up-regulated in mDCs cultured with AECs. Moreover, murine mucosal DCs from the lung expressed significantly higher levels of TLRs and NLRs compared to peripheral DCs from the spleen. These results indicate that AECs prime mDCs to enhance their immunogenicity, which could be one of the mechanisms that compensates for the immunosuppressive mucosal environment. CI - (c) 2017 British Society for Immunology. FAU - Agrawal, S AU - Agrawal S AD - Division of Basic and Clinical Immunology, Department of Medicine, Irvine, CA, USA. FAU - Srivastava, R AU - Srivastava R AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, Irvine, CA, USA. FAU - Rahmatpanah, F AU - Rahmatpanah F AD - Department of pathology, University of California, Irvine, Irvine, CA, USA. FAU - Madiraju, C AU - Madiraju C AD - Division of Basic and Clinical Immunology, Department of Medicine, Irvine, CA, USA. FAU - BenMohamed, L AU - BenMohamed L AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, Irvine, CA, USA. FAU - Agrawal, A AU - Agrawal A AUID- ORCID: 0000-0002-3323-9152 AD - Division of Basic and Clinical Immunology, Department of Medicine, Irvine, CA, USA. LA - eng GR - P30 CA062203/CA/NCI NIH HHS/United States GR - R01 AG045216/AG/NIA NIH HHS/United States GR - UL1 TR000153/TR/NCATS NIH HHS/United States GR - UL1 TR001414/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170522 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (NLR Proteins) RN - 0 (Toll-Like Receptors) SB - IM MH - Animals MH - Antigen Presentation MH - Bronchi/*cytology MH - Cell Differentiation MH - Cells, Cultured MH - Chemokines/genetics/immunology MH - Coculture Techniques MH - Cytokines/genetics/immunology MH - Dendritic Cells/*immunology MH - Epithelial Cells/*immunology MH - Genes, MHC Class II MH - Humans MH - Mice MH - Myeloid Cells/*immunology MH - NLR Proteins/genetics/metabolism MH - Toll-Like Receptors/genetics/immunology PMC - PMC5543474 OTO - NOTNLM OT - bronchial epithelial cells OT - chemokines OT - myeloid dendritic cells OT - pathogen recognition receptors EDAT- 2017/05/05 06:00 MHDA- 2017/10/17 06:00 PMCR- 2018/09/01 CRDT- 2017/05/05 06:00 PHST- 2017/04/25 00:00 [accepted] PHST- 2017/05/05 06:00 [pubmed] PHST- 2017/10/17 06:00 [medline] PHST- 2017/05/05 06:00 [entrez] PHST- 2018/09/01 00:00 [pmc-release] AID - CEI12983 [pii] AID - 10.1111/cei.12983 [doi] PST - ppublish SO - Clin Exp Immunol. 2017 Sep;189(3):279-289. doi: 10.1111/cei.12983. Epub 2017 May 22.