PMID- 19910049 OWN - NLM STAT- MEDLINE DCOM- 20100219 LR - 20211020 IS - 1872-9142 (Electronic) IS - 0161-5890 (Print) IS - 0161-5890 (Linking) VI - 47 IP - 4 DP - 2010 Jan TI - Reoxygenation of hypoxia-differentiated dentritic cells induces Th1 and Th17 cell differentiation. PG - 922-31 LID - 10.1016/j.molimm.2009.09.038 [doi] AB - Dendritic cells (DCs) are often exposed to various oxygen tensions under physiological and pathological conditions. However, the effects of various oxygen tensions on DC functions remain unclear. In this study, we showed that hypoxia-differentiated DCs expressed lower levels of MHC-II molecule, co-stimulatory molecules (CD80, CD86) and proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), but higher levels of immunoregulatory cytokine transforming growth factor-beta (TGF-beta) than normoxia-differentiated DCs. Unexpectedly, re-exposure of hypoxia-differentiated DCs to saturated oxygen (reoxygenation) completely restored their mature phenotype and function. Specifically, the reoxygenated DCs induced naive CD4(+) T cells to differentiate into Th1 and Th17 effector cells, but deceased the generation of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). The data indicate that hypoxic microenvironment suppresses the maturation and function of murine DCs. Reoxygenation of hypoxia-differentiated DCs however results in complete recovery of their mature phenotype and function, and has strong ability to drive immune response toward a proinflammatory direction, suggesting reoxygenated DCs may contribute to inflammation of ischemia-reperfusion injury. CI - Published by Elsevier Ltd. FAU - Wang, Qun AU - Wang Q AD - Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan 250012, China. FAU - Liu, Chunmei AU - Liu C FAU - Zhu, Faliang AU - Zhu F FAU - Liu, Fengming AU - Liu F FAU - Zhang, Pin AU - Zhang P FAU - Guo, Chun AU - Guo C FAU - Wang, Xiaoyan AU - Wang X FAU - Li, Haiyan AU - Li H FAU - Ma, Chunhong AU - Ma C FAU - Sun, Wensheng AU - Sun W FAU - Zhang, Yun AU - Zhang Y FAU - Chen, Wanjun AU - Chen W FAU - Zhang, Lining AU - Zhang L LA - eng GR - ZIA DE000101-06/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20091112 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (CD4 Antigens) RN - 0 (Cytokines) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - CD4 Antigens/immunology MH - Cell Differentiation/*drug effects MH - Cell Hypoxia/drug effects MH - Cell Proliferation/drug effects MH - Coculture Techniques MH - Cytokines/metabolism MH - Dendritic Cells/*cytology/*drug effects/immunology MH - Female MH - Forkhead Transcription Factors/immunology MH - Interleukin-2 Receptor alpha Subunit/immunology MH - Mice MH - Mice, Inbred BALB C MH - Oxygen/*pharmacology MH - Phenotype MH - T-Lymphocytes, Helper-Inducer/*cytology/*drug effects/immunology MH - T-Lymphocytes, Regulatory/cytology/drug effects/immunology MH - Th1 Cells/cytology/drug effects/immunology PMC - PMC2815172 MID - NIHMS158766 EDAT- 2009/11/17 06:00 MHDA- 2010/02/20 06:00 PMCR- 2011/01/01 CRDT- 2009/11/14 06:00 PHST- 2009/07/24 00:00 [received] PHST- 2009/09/24 00:00 [revised] PHST- 2009/09/30 00:00 [accepted] PHST- 2009/11/14 06:00 [entrez] PHST- 2009/11/17 06:00 [pubmed] PHST- 2010/02/20 06:00 [medline] PHST- 2011/01/01 00:00 [pmc-release] AID - S0161-5890(09)00752-4 [pii] AID - 10.1016/j.molimm.2009.09.038 [doi] PST - ppublish SO - Mol Immunol. 2010 Jan;47(4):922-31. doi: 10.1016/j.molimm.2009.09.038. Epub 2009 Nov 12.