Monocyte induction of IL-10 and down-regulation of IL-12 by iC3b deposited in ultraviolet-exposed human skin.
CD11b+ monocytic/macrophagic cells (Mo/Mph), which infiltrate into skin after UV irradiation, play an important role in UV-induced immunosuppression. Because in mice, blockade of CD11b (iC3b receptor) on monocytes and depletion of its ligand, iC3b, reverses UV-induced immunosuppression, we asked whether iC3b is deposited in human skin after UV, and whether iC3b can modulate the cytokine profile of Mo/Mph. Immunofluorescence studies revealed that iC3b was newly deposited in UV-exposed skin and was localized in apposition to infiltrating CD11b+ Mo/Mph. In addition, in situ hybridization studies showed that TNF-alpha mRNA was also induced in a similar microanatomic localization. To model the effects of these complex signals on infiltrating Mo/Mph following UV exposure, we then tested the effects of immobilized iC3b and TNF-alpha on resting blood monocytes. Both IL-10 mRNA synthesis and protein secretion were significantly induced by binding of iC3b in vitro and were synergistically increased by the presence of TNF-alpha. The effect was abrogated by a blocking Ab to CD11b, indicating CD11b-iC3b interaction. In contrast, iC3b binding resulted in suppression of IL-12 p40 mRNA and significantly inhibited the production of IL-12 p70 protein. Our studies thus define a novel mechanism for induction of tissue Mo/Mph into an IL-10high/IL-12low state via iC3b in combination with TNF-alpha.
Yoshida
Y
Y
Department of Dermatology, Case Western Reserve University, University Hospitals of Cleveland, OH 44106, USA.
Kang
K
K
Berger
M
M
Chen
G
G
Gilliam
A C
AC
Moser
A
A
Wu
L
L
Hammerberg
C
C
Cooper
K D
KD
D000328:Adult; D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology / Q000528:radiation effects; D003179:Complement C3b / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D015536:Down-Regulation / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D017403:In Situ Hybridization; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014466:Ultraviolet Rays
D018821:CD18 Antigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D003179:Complement C3b