Interleukin 10 decreases MICA expression on melanoma cell surface.
Natural-killer group 2, member D (NKG2D) binds to a variety of ligands, including the major histocompatibility complex (MHC) class I chain-related proteins (MIC) and UL16-binding proteins (ULBP). It is regarded as a co-activating receptor on NK cells, having an important role in the cell-mediated immune response to tumours. We studied the influence of interleukin (IL)-10 on the regulation of MIC and ULBP expression on melanoma cells, and its effect on the cytotoxic function of NK cells in vitro. Here, we show that, in the presence of IL-10, FMS mel and BL mel cell lines decreased MICA and ULBP2 surface expression, whereas MHC class I did not change substantially on the cell surface. MICA mRNA levels decreased in IL-10-treated FMS and IL-10-transduced BL cell lines. Interestingly, we observed that MICB surface expression and its mRNA levels increased upon IL-10 treatment in a melanoma cell line. These changes in NKG2D ligands surface expression patterns owing to IL-10 treatment resulted in an effect on lysis susceptibility mediated by lymphocyte-activated killer cells, as tumour cell lines that displayed a higher decrease of MICA on their surface had lower levels of lysis. In addition, expression of CD107a was downregulated on the surface of NK cells following stimulation with IL-10-treated FMS cells. Our results suggest a novel function for IL-10 in the modulation of NKG2D ligand expression and in the control of cytotoxicity mediated by NKG2D/NKG2D ligand axis.
Serrano
Antonio E
AE
Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Metropolitana, Chile.
Menares-Castillo
Evelyn
E
Garrido-Tapia
Macarena
M
Ribeiro
Carolina Hager
CH
Hernández
Carolina J
CJ
Mendoza-Naranjo
Ariadna
A
Gatica-Andrades
Marcela
M
Valenzuela-Diaz
Rodrigo
R
Zúñiga
Roberto
R
López
Mercedes N
MN
Salazar-Onfray
Flavio
F
Aguillón
Juan-Carlos
JC
Molina
María-Carmen
MC
D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008545:Melanoma / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D053701:Receptors, Interleukin-10; D016753:Interleukin-10