Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs

被引:174
作者
Bradley, C. Pierce [1 ]
Teng, Fei [1 ]
Felix, Krysta M. [1 ]
Sano, Teruyuki [2 ]
Naskar, Debdut [1 ]
Block, Katharine E. [3 ]
Huang, Haochu [3 ]
Knox, Kenneth S. [4 ]
Littman, Dan R. [2 ,5 ]
Wu, Hsin-Jung Joyce [1 ,6 ]
机构
[1] Univ Arizona, Dept Immunobiol, Tucson, AZ 85719 USA
[2] NYU, Sch Med, Mol Pathogenesis Program, Kimmel Ctr Biol & Med,Skirball Inst, New York, NY 10016 USA
[3] Univ Chicago, Dept Med, Sect Rheumatol, Chicago, IL 60637 USA
[4] Univ Arizona, Arizona Resp Ctr, Tucson, AZ 85719 USA
[5] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA
[6] Univ Arizona, Coll Med, Arizona Arthrit Ctr, Tucson, AZ 85719 USA
关键词
RECEPTOR-ALPHA-CHAINS; BETA ALLELIC EXCLUSION; T FOLLICULAR HELPER; RHEUMATOID-ARTHRITIS; T(H)17 CELLS; MICROBIOTA; INFECTION; RESPONSES; TRIGGERS; DISEASE;
D O I
10.1016/j.chom.2017.10.007
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gutlung crosstalk and dual TCR-based autoimmunity.
引用
收藏
页码:697 / +
页数:12
相关论文
共 47 条
[1]  
Alam SM, 1998, J IMMUNOL, V160, P3883
[2]   Mechanisms of disease: Molecular mimicry and autoimmunity. [J].
Albert, LJ ;
Inman, RD .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (27) :2068-2074
[3]   Cutting Edge: Intravascular Staining Redefines Lung CD8 T Cell Responses [J].
Anderson, Kristin G. ;
Sung, Heungsup ;
Skon, Cara N. ;
Lefrancois, Leo ;
Deisinger, Angela ;
Vezys, Vaiva ;
Masopust, David .
JOURNAL OF IMMUNOLOGY, 2012, 189 (06) :2702-2706
[4]   Incomplete TCR-β allelic exclusion accelerates spontaneous autoimmune arthritis in K/BxN TCR transgenic mice [J].
Auger, Jennifer L. ;
Haasken, Stefanie ;
Steinert, Elizabeth M. ;
Binstadt, Bryce A. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2012, 42 (09) :2354-2362
[5]   Emerging pathogenic links between microbiota and the gut-lung axis [J].
Budden, Kurtis F. ;
Gellatly, Shaan L. ;
Wood, David L. A. ;
Cooper, Matthew A. ;
Morrison, Mark ;
Hugenholtz, Philip ;
Hansbro, Philip M. .
NATURE REVIEWS MICROBIOLOGY, 2017, 15 (01) :55-63
[6]   Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells [J].
Califano, Danielle ;
Cho, Jonathan J. ;
Uddin, Mohammad N. ;
Lorentsen, Kyle J. ;
Yang, Qi ;
Bhandoola, Avinash ;
Li, Hongmin ;
Avram, Dorina .
IMMUNITY, 2015, 43 (02) :354-368
[7]   Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal [J].
Carlin, Leo M. ;
Stamatiades, Efstathios G. ;
Auffray, Cedric ;
Hanna, Richard N. ;
Glover, Leanne ;
Vizcay-Barrena, Gema ;
Hedrick, Catherine C. ;
Cook, H. Terence ;
Diebold, Sandra ;
Geissmann, Frederic .
CELL, 2013, 153 (02) :362-375
[8]   Evaluation of the percentage of peripheral T cells with two different T cell receptor α-chains and of their potential role in autoimmunity [J].
Corthay, A ;
Nandakumar, KS ;
Holmdahl, R .
JOURNAL OF AUTOIMMUNITY, 2001, 16 (04) :423-429
[9]   When and where does inflammation begin in rheumatoid arthritis? [J].
Demoruelle, M. Kristen ;
Deane, Kevin D. ;
Holers, V. Michael .
CURRENT OPINION IN RHEUMATOLOGY, 2014, 26 (01) :64-71
[10]   Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells [J].
Duerr, Claudia U. ;
McCarthy, Connor D. A. ;
Mindt, Barbara C. ;
Rubio, Manuel ;
Meli, Alexandre P. ;
Pothlichet, Julien ;
Eva, Megan M. ;
Gauchat, Jean-Francois ;
Qureshi, Salman T. ;
Mazer, Bruce D. ;
Mossman, Karen L. ;
Malo, Danielle ;
Gamero, Ana M. ;
Vidal, Silvia M. ;
King, Irah L. ;
Sarfati, Marika ;
Fritz, Joerg H. .
NATURE IMMUNOLOGY, 2016, 17 (01) :65-+