Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis.
IL-10 is a pleiotropic cytokine that inhibits several immune parameters, including Th1 cell-mediated immune responses, antigen presentation, and antigen-specific T cell proliferation. Recent data implicate IL-10 as a mediator of suppression of cell-mediated immunity induced by exposure to UVB radiation (280-320 nm). To investigate the effects of IL-10 on the cutaneous immune system, we engineered transgenic mice that overexpress viral IL-10 (vIL-10) in the epidermis. vIL-10 transgenic mice demonstrated a reduced number of I-A(+) epidermal and dermal cells and fewer I-A(+) hapten-bearing cells in regional lymph nodes after hapten painting of the skin. Reduced CD80 and CD86 expression by I-A(+) epidermal cells was also observed. vIL-10 transgenic mice demonstrated a smaller delayed-type hypersensitivity response to allogeneic cells upon challenge but had normal contact hypersensitivity to an epicutaneously applied hapten. Fresh epidermal cells from vIL-10 transgenic mice showed a decreased ability to stimulate allogeneic T cell proliferation, as did splenocytes. Additionally, chronic exposure of mice to UVB radiation led to the development of fewer skin tumors in vIL-10 mice than in WT controls, and vIL-10 transgenic mice had increased splenic NK cell activity against YAC-1targets. These findings support the concept that IL-10 is an important regulator of cutaneous immune function.
Ding
Wanhong
W
Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA.
Beissert
Stefan
S
Deng
Liang
L
Miranda
Edward
E
Cassetty
Christopher
C
Seiffert
Kristina
K
Campton
Kristina L
KL
Yan
Zhengmin
Z
Murphy
George F
GF
Bluestone
Jeffrey A
JA
Granstein
Richard D
RD
D000818:Animals; D001483:Base Sequence; D003602:Cytotoxicity, Immunologic; D004274:DNA, Recombinant / Q000235:genetics; D003877:Dermatitis, Contact; D015870:Gene Expression; D006241:Haptens / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*
C066460:BCRF1 protein, Human herpesvirus 4; D004274:DNA, Recombinant; D006241:Haptens; D012333:RNA, Messenger; D014764:Viral Proteins; D016753:Interleukin-10