Inclusive estimation of complex antigen presentation functions of monocyte-derived dendritic cells differentiated under normoxia and hypoxia conditions |
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Authors: | Toshitatsu?Ogino Hideya?Onishi Hiroyuki?Suzuki Takashi?Morisaki Masao?Tanaka Email author" target="_blank">Mitsuo?KatanoEmail author |
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Institution: | (1) Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan;(2) Fukuoka Cancer General Clinic, Fukuoka, Japan;(3) Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan; |
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Abstract: | Dendritic cells (DCs) generated from monocytes under 20% O2 are now used as therapeutic tools for cancer patients. However, the O2 concentration is between 3 and 0.5% in most tissues. We evaluated these complicated functions of DCs under oxygen tensions
mimicking in vivo situations. Immature DCs (imDCs) were generated from monocytes using IL-4 and GM-CSF under normoxia (20%
O2; N-imDCs) or hypoxia (1% O2; H-imDCs). Mature DCs (mDCs) were induced with LPS. DCs were further exposed to normoxia (N/N-DCs) or hypoxia (N/H-DCs and
H/H-DCs) conditions. Using a 2-D culture system, H-DCs were smaller in size than N-DCs, and H/H-DCs exhibited higher allo-T
cell stimulation ability than N/N-DCs and N/H-DCs. On the other hand, motility and phagocytic ability of H/H-DCs were significantly
lower than those of N/H-DCs and N/N-DCs. In a 3-D culture system, however, maturation of H/H-imDCs and N/H-imDCs was suppressed
compared with N/N-imDCs as a result of their decreased motility and phagocytosis. Interestingly, silencing of HIF-1α by RNA interference decreased CD83 expression without affecting any antigen presentation abilities except for the ability
to stimulate the allo-T cell population. Our data could help our understanding of DCs, especially therapeutic DCs, in vivo. |
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