STAT3 promotes CD1d-mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis

被引:10
作者
Iyer, Abhirami K. [1 ]
Liu, Jianyun [1 ]
Gallo, Richard M. [1 ]
Kaplan, Mark H. [1 ,2 ]
Brutkiewicz, Randy R. [1 ]
机构
[1] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
[2] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA
关键词
antigen presentation; Janus kinase; signal transducer and activation of transcription; signal transduction; KILLER T-CELLS; DENDRITIC CELLS; NKT CELLS; CATHEPSIN-S; CD1D; EFFECTOR; RECOGNITION; AUTOIMMUNE; INHIBITION; MOLECULES;
D O I
10.1111/imm.12521
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytokines that regulate the immune response signal through the Janus kinase / signal transducer and activation of transcription (JAK/STAT) pathway, but whether this pathway can regulate CD1d-mediated lipid antigen presentation to natural killer T (NKT) cells is unknown. Here, we found that STAT3 promotes antigen presentation by CD1d. Antigen-presenting cells (APCs) in which STAT3 expression was inhibited exhibited markedly reduced endogenous lipid antigen presentation to NKT cells without an impact on exogenous lipid antigen presentation by CD1d. Consistent with this observation, in APCs where STAT3 was knocked down, dramatically decreased levels of UDP glucose ceramide glucosyltransferase (UGCG), an enzyme involved in the first step of glycosphingolipid biosynthesis, were observed. Impaired lipid antigen presentation was reversed by ectopic expression of UGCG in STAT3-silenced CD1d(+) APCs. Hence, by controlling a fundamental step in CD1d-mediated lipid antigen presentation, STAT3 signalling promotes innate immune responses driven by CD1d.
引用
收藏
页码:444 / 455
页数:12
相关论文
共 65 条
[1]   Inhibition of CD1d-mediated antigen presentation by the transforming growth factor-β/Smad signalling pathway [J].
Bailey, Jennifer C. ;
Iyer, Abhirami K. ;
Renukaradhya, Gourapura J. ;
Lin, Yinling ;
Nguyen, Hoa ;
Brutkiewicz, Randy R. .
IMMUNOLOGY, 2014, 143 (04) :679-691
[2]   CD1 antigen presentation: how it works [J].
Barral, Duarte C. ;
Brenner, Michael B. .
NATURE REVIEWS IMMUNOLOGY, 2007, 7 (12) :929-941
[3]   The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses [J].
Bell, Bryan D. ;
Kitajima, Masayuki ;
Larson, Ryan P. ;
Stoklasek, Thomas A. ;
Pang, Kristen ;
Sakamoto, Kazuhito ;
Wagner, Kay-Uwe ;
Reizis, Boris ;
Hennighausen, Lothar ;
Ziegler, Steven F. .
NATURE IMMUNOLOGY, 2013, 14 (04) :364-371
[4]   Natural killer T cells: drivers or passengers in preventing human disease? [J].
Berzins, Stuart P. ;
Ritchie, David S. .
NATURE REVIEWS IMMUNOLOGY, 2014, 14 (09) :640-646
[5]   Presumed guilty: natural killer T cell defects and human disease [J].
Berzins, Stuart P. ;
Smyth, Mark J. ;
Baxter, Alan G. .
NATURE REVIEWS IMMUNOLOGY, 2011, 11 (02) :131-142
[6]   The Alpha and Omega of Galactosylceramides in T Cell Immune Function [J].
Birkholz, Alysia M. ;
Howell, Amy R. ;
Kronenberg, Mitchell .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (25) :15365-15370
[7]   Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions [J].
Brennan, Patrick J. ;
Brigl, Manfred ;
Brenner, Michael B. .
NATURE REVIEWS IMMUNOLOGY, 2013, 13 (02) :101-117
[8]   Synthetic iNKT cell-agonists as vaccine adjuvants finding the balance [J].
Cerundolo, Vincenzo ;
Barral, Patricia ;
Batista, Facundo D. .
CURRENT OPINION IN IMMUNOLOGY, 2010, 22 (03) :417-424
[9]   A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophages [J].
Chan, Lally L. Y. ;
Cheung, Benny K. W. ;
Li, James C. B. ;
Lau, Allan S. Y. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2010, 88 (02) :303-311
[10]   Role and Regulation of CD1d in Normal and Pathological B Cells [J].
Chaudhry, Mohammed S. ;
Karadimitris, Anastasios .
JOURNAL OF IMMUNOLOGY, 2014, 193 (10) :4761-4768