TLR7-mediated activation of XBP1 correlates with the IFNα production in humans

被引：15

作者：

Beisel, Claudia ^{[1
,2
,4
]}

Ziegler, Susanne ^{[1
]}

Zapater, Gloria Martrus ^{[1
,4
]}

Chapel, Anais ^{[1
]}

Griesbeck, Morgane ^{[3
]}

Hildebrandt, Heike ^{[1
]}

Lohse, Ansgar W. ^{[2
,4
]}

Altfeld, Marcus ^{[1
,4
]}

机构：

[1] Heinrich Pette Inst, Leibniz Inst Expt Virol, Martinistr 52, D-20251 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Infect Dis Unit, Dept Internal Med 1, Hamburg, Germany

[3] Hop La Pitie Salpetriere, Ctr Immunol & Infect Dis CIMI, Paris, France

[4] German Ctr Infect Res DZIF, Hamburg, Germany

来源：

CYTOKINE | 2017年 / 94卷

关键词：

XBP1; Toll-like receptor 7; Interferon alpha; UNFOLDED PROTEIN RESPONSE; INHIBITION; CELLS;

D O I：

10.1016/j.cyto.2017.04.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The transcription factor X-box binding protein 1 (XBP1) represents a key component of the endoplasmatic reticulum (ER) stress response and is required for the production of several pro-inflammatory cytokines. XBP1 is furthermore essential for the development and survival of plasmacytoid dendritic cells (pDCs), and has recently been suggested to be involved in toll-like receptor (TLR) 2/4 signaling. Activation of TLR7 on pDCs results in an upregulation of pro-inflammatory cytokines, such as type I interferons (IFN-I), and has been implicated in several autoimmune and inflammatory diseases, but the role of XBP1 in this process remains unknown. Here, we show that signaling via TLR7 leads to an upregulation of XBP1 and IFN alpha-production. XBP1 mRNA expression levels positively correlated with the production of IFN alpha, while blocking of XBP1 mRNA splicing significantly reduced mRNA transcripts of IFNa. In conclusion, these data suggest a central role of XBP1 in TLR7-induced IFNa production and identify XBP1 as a potential novel therapeutic target in IFN alpha-driven autoimmune and inflammatory diseases.

引用

页码：55 / 58

页数：4

共 13 条

[1] The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule [J].

Cross, Benedict C. S. ;

Bond, Peter J. ;

Sadowski, Pawel G. ;

Jha, Babal Kant ;

Zak, Jaroslav ;

Goodman, Jonathan M. ;

Silverman, Robert H. ;

Neubert, Thomas A. ;

Baxendale, Ian R. ;

Ron, David ;

Harding, Heather P. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (15) :E869-E878

[2] Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women [J].

Griesbeck, Morgane ;

Ziegler, Susanne ;

Laffont, Sophie ;

Smith, Nikaia ;

Chauveau, Lise ;

Tomezsko, Phillip ;

Sharei, Armon ;

Kourjian, Georgio ;

Porichis, Filippos ;

Hart, Meghan ;

Palmer, Christine D. ;

Sirignano, Michael ;

Beisel, Claudia ;

Hildebrandt, Heike ;

Cenac, Claire ;

Villani, Alexandra-Chloe ;

Diefenbach, Thomas J. ;

Le Gall, Sylvie ;

Schwartz, Olivier ;

Herbeuval, Jean-Philippe ;

Autran, Brigitte ;

Guery, Jean-Charles ;

Chang, J. Judy ;

Altfeld, Marcus .

JOURNAL OF IMMUNOLOGY, 2015, 195 (11) :5327-5336

[3] Targeting the unfolded protein response in disease [J].

Hetz, Claudio ;

Chevet, Eric ;

Harding, Heather P. .

NATURE REVIEWS DRUG DISCOVERY, 2013, 12 (09) :703-719

[4] The transcription factor XBP-1 is essential for the development and survival of dendritic cells [J].

Iwakoshi, Neal N. ;

Pypaert, Marc ;

Glimcher, Laurie H. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (10) :2267-2275

[5] Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases [J].

Kanno, Atsuo ;

Tanimura, Natsuko ;

Ishizaki, Masayuki ;

Ohko, Kentaro ;

Motoi, Yuji ;

Onji, Masahiro ;

Fukui, Ryutaro ;

Shimozato, Takaichi ;

Yamamoto, Kazuhide ;

Shibata, Takuma ;

Sano, Shigetoshi ;

Sugahara-Tobinai, Akiko ;

Takai, Toshiyuki ;

Ohto, Umeharu ;

Shimizu, Toshiyuki ;

Saitoh, Shin-ichiroh ;

Miyake, Kensuke .

NATURE COMMUNICATIONS, 2015, 6

[6] XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response [J].

Lee, AH ;

Iwakoshi, NN ;

Glimcher, LH .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (21) :7448-7459

[7] Endoplasmic Reticulum Stress Regulates the Innate Immunity Critical Transcription Factor IRF3 [J].

Liu, Yi-Ping ;

Zeng, Ling ;

Tian, Austin ;

Bomkamp, Ashley ;

Rivera, Daniel ;

Gutman, Delia ;

Barber, Glen N. ;

Olson, Julie K. ;

Smith, Judith A. .

JOURNAL OF IMMUNOLOGY, 2012, 189 (09) :4630-4639

[8] TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages [J].

Martinon, Fabio ;

Chen, Xi ;

Lee, Ann-Hwee ;

Glimcher, Laurie H. .

NATURE IMMUNOLOGY, 2010, 11 (05) :411-U71

[9] Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma [J].

Mimura, Naoya ;

Fulciniti, Mariateresa ;

Gorgun, Gullu ;

Tai, Tzu ;

Cirstea, Diana ;

Santo, Loredana ;

Hu, Yiguo ;

Fabre, Claire ;

Ohguchi, Jiro Minami Hiroto ;

Kiziltepe, Tanyel ;

Ikeda, Hiroshi ;

Kawano, Yutaka ;

French, Maureen ;

Blumenthal, Martina ;

Tam, Victor ;

Kertesz, Nathalie L. ;

Malyankar, Uriel M. ;

Hokenson, Mark ;

Pham, Tuan ;

Zeng, Qingping ;

Patterson, John B. ;

Richardson, Paul G. ;

Munshi, Nikhil C. ;

Anderson, Kenneth C. .

BLOOD, 2012, 119 (24) :5772-5781

[10] Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma [J].

Papandreou, Ioanna ;

Denko, Nicholas C. ;

Olson, Michael ;

Van Melckebeke, Heleen ;

Lust, Sofie ;

Tam, Arvin ;

Solow-Cordero, David E. ;

Bouley, Donna M. ;

Offner, Fritz ;

Niwa, Maho ;

Koong, Albert C. .

BLOOD, 2011, 117 (04) :1311-1314

← 1 2 →