PMID- 17187851 OWN - NLM STAT- MEDLINE DCOM- 20070312 LR - 20211203 IS - 0091-6749 (Print) IS - 0091-6749 (Linking) VI - 119 IP - 2 DP - 2007 Feb TI - Ambient particulate matter directs nonclassic dendritic cell activation and a mixed TH1/TH2-like cytokine response by naive CD4+ T cells. PG - 488-97 AB - BACKGROUND: Dendritic cells (DCs) translate environmental cues into T-cell activating signals, and are centrally involved in allergic airway inflammation. Ambient particulate matter (APM) is ubiquitous and associated with allergic diseases, but it is unknown whether APM directly activates DCs. OBJECTIVE: To study comprehensively the effects of APM on myeloid DC phenotype and function. METHODS: Development of DC was modeled using human CD34(+) progenitor cells. APM was collected from ambient outdoor air in Baltimore city. We studied the effects of APM on DC activation in vitro, compared with LPS. RESULTS: Ambient particulate matter enhanced DC expression of costimulatory receptors but suppressed the expression of both the endocytosis receptor CD206 and uptake of fluorescein isothiocyanate-conjugated dextran. The expression of the Toll-like pattern-recognition receptors Toll-like receptor 2 and Toll-like receptor 4 was also blunted. APM-exposed DCs secreted less IL-12 and IL-6 but exhibited increased secretion of IL-18 and IL-10 compared with LPS stimulation. A T(H)2-like pattern of cytokine production was seen in cocultures of APM-stimulated DCs and alloreactive naive CD4(+) T cells where the IL-13 to IFN-gamma ratio was reversed. This contrasted with the T(H)1 polarizing effects of LPS on DCs. CONCLUSION: We report for the first time that APM-exposed DCs direct a complex T(H)1/T(H)2-like pattern of T-cell activation by mechanisms that involve nonclassic activation of DCs. CLINICAL IMPLICATIONS: Inhaled APM can act directly on DCs as a danger signal to direct a proallergic pattern of innate immune activation. FAU - Williams, Marc A AU - Williams MA AD - Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. marc_williams@urmc.rochester.edu FAU - Porter, Michael AU - Porter M FAU - Horton, Maureen AU - Horton M FAU - Guo, Jia AU - Guo J FAU - Roman, Jessica AU - Roman J FAU - Williams, D'Ann AU - Williams D FAU - Breysse, Patrick AU - Breysse P FAU - Georas, Steve N AU - Georas SN LA - eng GR - P01 ES09606/ES/NIEHS NIH HHS/United States GR - P30 ES03819/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20061221 PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Cytokines) RN - 0 (Lectins, C-Type) RN - 0 (Mannose Receptor) RN - 0 (Mannose-Binding Lectins) RN - 0 (Particulate Matter) RN - 0 (Receptors, Cell Surface) RN - 0 (TLR2 protein, human) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Antigen Presentation MH - CD4-Positive T-Lymphocytes/*immunology MH - Cytokines/*biosynthesis MH - Dendritic Cells/*physiology MH - Endocytosis MH - Humans MH - Lectins, C-Type/analysis MH - Leukocyte Common Antigens/analysis MH - Mannose Receptor MH - Mannose-Binding Lectins/analysis MH - Particulate Matter/*toxicity MH - Receptors, Cell Surface/analysis MH - Th1 Cells/*immunology MH - Th2 Cells/*immunology MH - Toll-Like Receptor 2/analysis MH - Toll-Like Receptor 4/analysis EDAT- 2006/12/26 09:00 MHDA- 2007/03/14 09:00 CRDT- 2006/12/26 09:00 PHST- 2006/02/17 00:00 [received] PHST- 2006/09/29 00:00 [revised] PHST- 2006/10/11 00:00 [accepted] PHST- 2006/12/26 09:00 [pubmed] PHST- 2007/03/14 09:00 [medline] PHST- 2006/12/26 09:00 [entrez] AID - S0091-6749(06)02218-4 [pii] AID - 10.1016/j.jaci.2006.10.022 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2007 Feb;119(2):488-97. doi: 10.1016/j.jaci.2006.10.022. Epub 2006 Dec 21.