TY - JOUR
T1 - Double-stranded RNA-exposed human keratinocytes promote Th1 responses by inducing a type-1 polarized phenotype in dendritic cells: Role of keratinocyte-derived tumor necrosis factor alpha, type I interferons, and interleukin-18
AU - Lebre, M. Cristina
AU - Antons, Jeanine C.
AU - Kalinski, Pawel
AU - Schuitemaker, Joost H. N.
AU - van Capel, Toni M. M.
AU - Kapsenberg, Martien L.
AU - de Jong, Esther C.
PY - 2003
Y1 - 2003
N2 - Dendritic cells play a key role in establishing the class of immune response against invading pathogens. Upon engagement with double-stranded RNA, a major bioactive constituent of many virus types, immature dendritic cells develop into type 1 immunostimulatory dendritic cells that promote Th1 responses. Immature dendritic cells reside in the epithelia and are in close contact with keratinocytes. We studied to what extent dendritic cells can also adopt a type 1 immunostimulatory dendritic cell phenotype indirectly, as a result of the interaction with keratinocytes responding to double-stranded RNA. In contrast to supernatants from keratinocytes activated by the combination of tumor necrosis factor alpha and interleukin-1beta, supernatants from keratinocytes activated by synthetic double-stranded RNA, polyriboinosinic polyribocytidylic acid, comprised tumor necrosis factor alpha and type I interferons, which induced maturation of human monocyte-derived immature dendritic cells. In addition, dendritic cells matured in the presence of these supernatants strongly biased the development of Th1 cells from naive Th cells. This bias was dependent on keratinocyte-derived interferon-alpha/beta and interleukin-18, as neutralization of both interferon-alpha/beta and interleukin-18 in the keratinocyte culture supernatant reduced the development of interferon-gamma-producing Th cells. These findings suggest that keratinocytes can contribute to the development of selective Th1/Th2 responses through the induction of maturation and functional polarization of dendritic cells, indicating a novel role for keratinocytes as initiators and regulators of cutaneous T-cell-mediated inflammation. In addition, these results support the concept that, in addition to direct interaction with pathogens, dendritic cells may also be activated and primed by pathogen indirectly, via the effect of resident tissue cells responding to pathogen
AB - Dendritic cells play a key role in establishing the class of immune response against invading pathogens. Upon engagement with double-stranded RNA, a major bioactive constituent of many virus types, immature dendritic cells develop into type 1 immunostimulatory dendritic cells that promote Th1 responses. Immature dendritic cells reside in the epithelia and are in close contact with keratinocytes. We studied to what extent dendritic cells can also adopt a type 1 immunostimulatory dendritic cell phenotype indirectly, as a result of the interaction with keratinocytes responding to double-stranded RNA. In contrast to supernatants from keratinocytes activated by the combination of tumor necrosis factor alpha and interleukin-1beta, supernatants from keratinocytes activated by synthetic double-stranded RNA, polyriboinosinic polyribocytidylic acid, comprised tumor necrosis factor alpha and type I interferons, which induced maturation of human monocyte-derived immature dendritic cells. In addition, dendritic cells matured in the presence of these supernatants strongly biased the development of Th1 cells from naive Th cells. This bias was dependent on keratinocyte-derived interferon-alpha/beta and interleukin-18, as neutralization of both interferon-alpha/beta and interleukin-18 in the keratinocyte culture supernatant reduced the development of interferon-gamma-producing Th cells. These findings suggest that keratinocytes can contribute to the development of selective Th1/Th2 responses through the induction of maturation and functional polarization of dendritic cells, indicating a novel role for keratinocytes as initiators and regulators of cutaneous T-cell-mediated inflammation. In addition, these results support the concept that, in addition to direct interaction with pathogens, dendritic cells may also be activated and primed by pathogen indirectly, via the effect of resident tissue cells responding to pathogen
U2 - https://doi.org/10.1046/j.1523-1747.2003.12245.x
DO - https://doi.org/10.1046/j.1523-1747.2003.12245.x
M3 - Article
C2 - 12787126
SN - 0022-202X
VL - 120
SP - 990
EP - 997
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -