Reoxygenation of hypoxia-differentiated dentritic cells induces Th1 and Th17 cell differentiation.
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 naïve 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.
Wang
Qun
Q
Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan 250012, China.
Liu
Chunmei
C
Zhu
Faliang
F
Liu
Fengming
F
Zhang
Pin
P
Guo
Chun
C
Wang
Xiaoyan
X
Li
Haiyan
H
Ma
Chunhong
C
Sun
Wensheng
W
Zhang
Yun
Y
Chen
Wanjun
W
Zhang
Lining
L
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000494:pharmacology*; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D010100:Oxygen