The cellular and molecular determinants of emphysematous destruction in COPD

被引:57
作者
Suzuki, Masaru [1 ,2 ,5 ,6 ]
Sze, Marc A. [1 ,2 ]
Campbell, Joshua D. [3 ]
Ii, John F. Brothers [3 ]
Lenburg, Marc E. [3 ]
McDonough, John E. [1 ,2 ]
Elliott, W. Mark [1 ,2 ]
Cooper, Joel D. [4 ]
Spira, Avrum [3 ]
Hogg, James C. [1 ,2 ]
机构
[1] Univ British Columbia, Dept Med, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada
[2] Univ British Columbia, Dept Pathol & Lab Med, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada
[3] Boston Univ, Sch Med, Dept Med, Div Computat Biomed, Boston, MA 02118 USA
[4] Hosp Univ Penn, Div Thorac Surg, 3400 Spruce St, Philadelphia, PA 19104 USA
[5] Hokkaido Univ, Fac Med, Dept Resp Med, Sapporo, Hokkaido, Japan
[6] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan
基金
加拿大健康研究院; 美国国家卫生研究院;
关键词
OBSTRUCTIVE PULMONARY-DISEASE; INNATE LYMPHOID-CELLS; SMALL-AIRWAY OBSTRUCTION; CHRONIC-BRONCHITIS; DENDRITIC CELLS; T-LYMPHOCYTES; INFLAMMATION;
D O I
10.1038/s41598-017-10126-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The introduction of microCT has made it possible to show that the terminal bronchioles are narrowed and destroyed before the onset of emphysematous destruction in COPD. This report extends those observations to the cellular and molecular level in the centrilobular phenotype of emphysematous destruction in lungs donated by persons with very severe COPD (n = 4) treated by lung transplantation with unused donor lungs (n = 4) serving as controls. These lung specimens provided companion samples to those previously examined by microCT (n = 61) that we examined using quantitative histology (n = 61) and gene expression profiling (n = 48). The histological analysis showed that remodeling and destruction of the bronchiolar and alveolar tissue is associated with macrophage, CD4, CD8, and B cell infiltration with increased formation of tertiary lymphoid organs. Moreover, gene set enrichment analysis showed that genes known to be expressed by natural killer (NK), lymphoid tissue inducer (LTi), and innate lymphoid cell 1 (ILC1) cells, but not ILC2 or ILC3 cells, were enriched in the expression profiles associated with CD4, CD8, and B cell infiltration. Based on these findings, we postulate that the centrilobular phenotype of emphysematous destruction COPD is driven by a Th1 response activated by infiltrating ILC1, NK, and LTi cells.
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页数:9
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共 44 条
[31]   Innate lymphoid cells: critical regulators of allergic inflammation and tissue repair in the lung [J].
Monticelli, Laurel A. ;
Sonnenberg, Gregory F. ;
Artis, David .
CURRENT OPINION IN IMMUNOLOGY, 2012, 24 (03) :284-289
[32]   Exploring the full spectrum of macrophage activation [J].
Mosser, David M. ;
Edwards, Justin P. .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (12) :958-969
[33]   Inflammation in bronchial biopsies of subjects with chronic bronchitis: Inverse relationship of CD8(+) T lymphocytes with FEV(1) [J].
OShaughnessy, TC ;
Ansari, TW ;
Barnes, NC ;
Jeffery, PK .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 155 (03) :852-857
[34]   New friendships and old feuds: relationships between innate lymphoid cells and microbial communities [J].
Philip, Naomi H. ;
Artis, David .
IMMUNOLOGY AND CELL BIOLOGY, 2013, 91 (03) :225-231
[35]   The WFDC1 gene: role in wound response and tissue homoeostasis [J].
Ressler, Steven J. ;
Rowley, David R. .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2011, 39 :1455-1459
[36]   Macrophage diversity in renal injury and repair [J].
Ricardo, Sharon D. ;
van Goor, Harry ;
Eddy, Allison A. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (11) :3522-3530
[37]   ACTIVATED LYMPHOCYTES-T AND MACROPHAGES IN BRONCHIAL-MUCOSA OF SUBJECTS WITH CHRONIC-BRONCHITIS [J].
SAETTA, M ;
DISTEFANO, A ;
MAESTRELLI, P ;
FERRARESSO, A ;
DRIGO, R ;
POTENA, A ;
CIACCIA, A ;
FABBRI, LM .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1993, 147 (02) :301-306
[38]   Contingent gene regulatory networks and B cell fate specification [J].
Singh, H ;
Medina, KL ;
Pongubala, JMR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (14) :4949-4953
[39]   Innate lymphoid cells - a proposal for uniform nomenclature [J].
Spits, Hergen ;
Artis, David ;
Colonna, Marco ;
Diefenbach, Andreas ;
Di Santo, James P. ;
Eberl, Gerard ;
Koyasu, Shigeo ;
Locksley, Richard M. ;
McKenzie, Andrew N. J. ;
Mebius, Reina E. ;
Powrie, Fiona ;
Vivier, Eric .
NATURE REVIEWS IMMUNOLOGY, 2013, 13 (02) :145-149
[40]   Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles [J].
Subramanian, A ;
Tamayo, P ;
Mootha, VK ;
Mukherjee, S ;
Ebert, BL ;
Gillette, MA ;
Paulovich, A ;
Pomeroy, SL ;
Golub, TR ;
Lander, ES ;
Mesirov, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15545-15550