Variety of endosomal TLRs and Interferons (IFN-α, IFN-β, IFN-γ) expression profiles in patients with SLE, SSc and MCTD

被引:21
作者
Paradowska-Gorycka, A. [1 ]
Wajda, A. [1 ]
Stypinska, B. [1 ]
Walczuk, E. [1 ]
Rzeszotarska, E. [1 ]
Walczyk, M. [2 ]
Haladyj, E. [3 ]
Romanowska-Prochnicka, K. [2 ,4 ]
Felis-Giemza, A. [2 ]
Lewandowska, A. [2 ]
Olesinska, M. [2 ]
机构
[1] Natl Inst Geriatr Rheumatol & Rehabil, Dept Mol Biol, Spartanska 1, PL-02637 Warsaw, Poland
[2] Natl Inst Geriatr Rheumatol & Rehabil, Dept Connect Tissue Dis, Warsaw, Poland
[3] Eli Lilly & Co, Indianapolis, IN 46285 USA
[4] Med Univ Warsaw, Ctr Preclin Res & Technol CEPT, Dept Gen & Expt Pathol, Warsaw, Poland
关键词
connective tissue disease; expression; interferon; pathogenesis; TLR;
D O I
10.1111/cei.13566
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We investigated Toll-like receptor (TLR)-3/-7/-8/-9 and interferon (IFN)-alpha/beta/gamma mRNA expression in whole blood and serum IFN-alpha/beta/gamma levels in patients with mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) and in healthy subjects to assess the association between the TLR-IFN expression and severity of and susceptibility to diseases, and identify potential biomarkers. Expression of the IFN-gamma, TLR-3 and TLR-8 was detected only in SLE patients. TLR-7, IFN-alpha and IFN-beta expression was highest in SLE, while TLR-9 expression was highest in SSc patients. In SLE and MCTD patients a strong correlation was observed between TLR-7 and IFN-alpha expression and IFN-beta and IFN-alpha expression. In MCTD patients, negative correlation between IFN-alpha and TLR-9 and TLR-7 and TLR-9 was revealed. TLR-9 expression in anti-U1-70k-negative, anti-C negative and anti-SmB-negative MCTD patients was higher than in MCTD-positive patients. We observed negative correlations between serum IFN-alpha levels and TLR-7 expression and C3 and C4 levels in SLE patients. In SLE patients we observed that with increased IFN-gamma, TLR-3 and TLR-8 expression increased the value of C3 and C4. Our results confirmed that the endosomal TLR-IFN pathway seems to be more important in SLE than in MCTD or SSc, and that IFN-alpha and IFN-beta may be possible biomarkers for SLE.
引用
收藏
页码:49 / 63
页数:15
相关论文
共 67 条
[1]  
Ahmed, 2013, INNOVAIT, V6, P159
[2]   Systemic Sclerosis and Lupus Points in an Interferon-Mediated Continuum [J].
Assassi, Shervin ;
Mayes, Maureen D. ;
Arnett, Frank C. ;
Gourh, Pravitt ;
Agarwal, Sandeep K. ;
McNearney, Terry A. ;
Chaussabel, Damien ;
Oommen, Nancy ;
Fischbach, Michael ;
Shah, Kairav R. ;
Charles, Julio ;
Pascual, Virginia ;
Reveille, John D. ;
Tan, Filemon K. .
ARTHRITIS AND RHEUMATISM, 2010, 62 (02) :589-598
[3]   Interferon-β inhibits bleomycin-induced lung fibrosis by decreasing transforming growth factor-β and thrombospondin [J].
Azuma, A ;
Li, YJ ;
Abe, S ;
Usuki, J ;
Matsuda, K ;
Henmi, S ;
Miyauchi, Y ;
Ueda, K ;
Izawa, A ;
Sone, S ;
Hashimoto, S ;
Kudoh, S .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2005, 32 (02) :93-98
[4]   Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus [J].
Baechler, EC ;
Batliwalla, FM ;
Karypis, G ;
Gaffney, PM ;
Ortmann, WA ;
Espe, KJ ;
Shark, KB ;
Grande, WJ ;
Hughes, KM ;
Kapur, V ;
Gregersen, PK ;
Behrens, TW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2610-2615
[5]   Interferon target-gene expression and epigenomic signatures in health and disease [J].
Barrat, Franck J. ;
Crow, Mary K. ;
Ivashkiv, Lionel B. .
NATURE IMMUNOLOGY, 2019, 20 (12) :1574-1583
[6]   Interferon and granulopoiesis signatures in systemic lupus erythematosus blood [J].
Bennett, L ;
Palucka, AK ;
Arce, E ;
Cantrell, V ;
Borvak, J ;
Banchereau, J ;
Pascual, V .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (06) :711-723
[7]   TLR9 Deficiency Leads to Accelerated Renal Disease and Myeloid Lineage Abnormalities in Pristane-Induced Murine Lupus [J].
Bossaller, Lukas ;
Christ, Anette ;
Pelka, Karin ;
Nundel, Kerstin ;
Chiang, Ping-I ;
Pang, Catherine ;
Mishra, Neha ;
Busto, Patricia ;
Bonegio, Ramon G. ;
Schmidt, Reinhold Ernst ;
Latz, Eicke ;
Marshak-Rothstein, Ann .
JOURNAL OF IMMUNOLOGY, 2016, 197 (04) :1044-1053
[8]   TLR7 and TLR9 in SLE: when sensing self goes wrong [J].
Celhar, T. ;
Magalhes, R. ;
Fairhurst, A-M. .
IMMUNOLOGIC RESEARCH, 2012, 53 (1-3) :58-77
[9]   Distinct Autoantibody Profiles in Systemic Lupus Erythematosus Patients are Selectively Associated with TLR7 and TLR9 Upregulation [J].
Chauhan, Sudhir Kumar ;
Singh, Vikas Vikram ;
Rai, Richa ;
Rai, Madhukar ;
Rai, Geeta .
JOURNAL OF CLINICAL IMMUNOLOGY, 2013, 33 (05) :954-964
[10]   Toll-Like Receptor Pathways in Autoimmune Diseases [J].
Chen, Ji-Qing ;
Szodoray, Peter ;
Zeher, Margit .
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, 2016, 50 (01) :1-17