دورية أكاديمية
Macrophage and CD8 T cell discordance are associated with acute lung allograft dysfunction progression.
| العنوان: | Macrophage and CD8 T cell discordance are associated with acute lung allograft dysfunction progression. |
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| المؤلفون: | Calabrese DR; Department of Medicine, University of California, San Francisco, California; Medical Service, Veterans Affairs Health Care System, San Francisco, California. Electronic address: daniel.calabrese@ucsf.edu., Ekstrand CA; Department of Pathology, University of California, San Francisco, California., Yellamilli S; Department of Pathology, University of California, San Francisco, California., Singer JP; Department of Medicine, University of California, San Francisco, California., Hays SR; Department of Medicine, University of California, San Francisco, California., Leard LE; Department of Medicine, University of California, San Francisco, California., Shah RJ; Department of Medicine, University of California, San Francisco, California., Venado A; Department of Medicine, University of California, San Francisco, California., Kolaitis NA; Department of Medicine, University of California, San Francisco, California., Perez A; Department of Medicine, University of California, San Francisco, California., Combes A; Department of Pathology, University of California, San Francisco, California., Greenland JR; Department of Medicine, University of California, San Francisco, California; Medical Service, Veterans Affairs Health Care System, San Francisco, California. |
| المصدر: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2024 Jul; Vol. 43 (7), pp. 1074-1086. Date of Electronic Publication: 2024 Feb 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 9102703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3117 (Electronic) Linking ISSN: 10532498 NLM ISO Abbreviation: J Heart Lung Transplant Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : New York, NY : Elsevier Original Publication: St. Louis, Mo. : Mosby-Year Book, Inc., c1991- |
| مواضيع طبية MeSH: | Lung Transplantation*/adverse effects , CD8-Positive T-Lymphocytes*/immunology , Macrophages*/immunology , Macrophages*/metabolism , Disease Progression*, Humans ; Male ; Middle Aged ; Female ; Prospective Studies ; Bronchoalveolar Lavage Fluid/cytology ; Allografts ; Graft Rejection/immunology ; Adult ; Acute Disease ; Primary Graft Dysfunction/immunology |
| مستخلص: | Background: Acute lung allograft dysfunction (ALAD) is an imprecise syndrome denoting concern for the onset of chronic lung allograft dysfunction (CLAD). Mechanistic biomarkers are needed that stratify risk of ALAD progression to CLAD. We hypothesized that single cell investigation of bronchoalveolar lavage (BAL) cells at the time of ALAD would identify immune cells linked to progressive graft dysfunction. Methods: We prospectively collected BAL from consenting lung transplant recipients for single cell RNA sequencing. ALAD was defined by a ≥10% decrease in FEV Results: BAL was assessed for 17 ALAD cases with subsequent decline (ALAD declined), 13 ALAD cases that resolved (ALAD recovered), and 15 cases with stable lung function. We observed broad differences in frequencies of the 26 unique cell populations across groups (p = 0.02). A CD8 T cell (p = 0.04) and a macrophage cluster (p = 0.01) best identified ALAD declined from the ALAD recovered and stable groups. This macrophage cluster was distinguished by an anti-inflammatory signature and the CD8 T cell cluster resembled a Tissue Resident Memory subset. Anti-inflammatory macrophages signaled to activated CD8 T cells via class I HLA, fibronectin, and galectin pathways (p < 0.05 for each). Recipients with discordance between these cells had a nearly 5-fold increased risk of severe graft dysfunction or death (HR 4.6, 95% CI 1.1-19.2, adjusted p = 0.03). We validated these key findings in 2 public lung transplant genomic datasets. Conclusions: BAL anti-inflammatory macrophages may protect against CLAD by suppressing CD8 T cells. These populations merit functional and longitudinal assessment in additional cohorts. Competing Interests: Conflict of interest The authors declare no relevant conflicts of interest. (Published by Elsevier Inc.) |
| References: | Nature. 2021 Mar;591(7848):124-130. (PMID: 33494096) J Clin Invest. 2022 Oct 3;132(19):. (PMID: 36189800) Sci Immunol. 2019 Mar 8;4(33):. (PMID: 30850393) J Med Econ. 2022 Jan-Dec;25(1):230-237. (PMID: 35068310) ERJ Open Res. 2023 May 30;9(3):. (PMID: 37260458) Am J Pathol. 2006 Sep;169(3):916-26. (PMID: 16936266) Transplantation. 2016 Sep;100(9):1803-14. (PMID: 27257997) J Heart Lung Transplant. 2021 Oct;40(10):1060-1072. (PMID: 34446355) Transplantation. 2010 Sep 15;90(5):540-6. (PMID: 20628341) Thorac Surg Clin. 2022 May;32(2):231-242. (PMID: 35512941) J Thorac Dis. 2017 Aug;9(8):2650-2659. (PMID: 28932572) Lancet. 2008 Nov 22;372(9652):1828-34. (PMID: 18842294) J Heart Lung Transplant. 2022 Apr;41(4):458-466. (PMID: 35063338) J Heart Lung Transplant. 2019 Aug;38(8):845-855. (PMID: 31122726) Transplantation. 2016 Oct;100(10):2090-8. (PMID: 27077597) Blood. 2016 Aug 25;128(8):e20-31. (PMID: 27365425) J Heart Lung Transplant. 2018 Jun;37(6):770-781. (PMID: 29571601) Circ Res. 2016 Jul 22;119(3):414-7. (PMID: 27458196) Am J Respir Crit Care Med. 2021 May 15;203(10):1230-1244. (PMID: 33306940) Mucosal Immunol. 2021 Jan;14(1):92-99. (PMID: 32518368) J Exp Med. 2022 Apr 4;219(4):. (PMID: 35285873) Am J Respir Cell Mol Biol. 2020 Oct;63(4):490-501. (PMID: 32551854) J Heart Lung Transplant. 2001 Oct;20(10):1064-74. (PMID: 11595561) PLoS One. 2018 Oct 5;13(10):e0205107. (PMID: 30289917) Am J Transplant. 2021 Jan;21(1):362-371. (PMID: 32885581) Immunology. 2012 Apr;135(4):287-98. (PMID: 22117697) Transplantation. 2019 Mar;103(3):493-501. (PMID: 30211828) J Gen Virol. 1994 Sep;75 ( Pt 9):2329-36. (PMID: 8077931) Am J Respir Crit Care Med. 2020 Aug 15;202(4):576-585. (PMID: 32379979) J Heart Lung Transplant. 2019 May;38(5):493-503. (PMID: 30962148) Transplantation. 2017 Oct;101(10):2469-2476. (PMID: 28926522) Am J Respir Crit Care Med. 2013 Mar 1;187(5):527-34. (PMID: 23306540) Nat Rev Immunol. 2022 May;22(5):283-293. (PMID: 34480118) Clin Transplant. 2018 Aug;32(8):e13332. (PMID: 29920787) Ann Am Thorac Soc. 2019 Jan;16(1):22-28. (PMID: 30230362) Int J Biol Sci. 2022 Aug 8;18(13):5168-5184. (PMID: 35982894) Front Immunol. 2019 Jul 17;10:1681. (PMID: 31379869) PLoS One. 2017 Jan 19;12(1):e0169894. (PMID: 28103284) JCI Insight. 2022 Dec 22;7(24):. (PMID: 36346670) J Heart Lung Transplant. 2014 Feb;33(2):127-33. (PMID: 24374027) Microsc Res Tech. 2010 Jun;73(6):579-82. (PMID: 19941295) Am J Transplant. 2017 Jun;17(6):1637-1648. (PMID: 27931084) Immunology. 2022 May;166(1):17-37. (PMID: 35137398) Am J Respir Cell Mol Biol. 2006 Jan;34(1):108-18. (PMID: 16195540) Nature. 2021 Feb;590(7847):635-641. (PMID: 33429418) J Heart Lung Transplant. 2022 Nov;41(11):1556-1569. (PMID: 35691795) Am J Transplant. 2023 Jan;23(1):37-44. (PMID: 36695619) JCI Insight. 2023 Mar 22;8(6):. (PMID: 36946463) J Exp Med. 2019 Dec 2;216(12):2748-2762. (PMID: 31558615) |
| معلومات مُعتمدة: | I01 CX002011 United States CX CSRD VA; R01 HL151552 United States HL NHLBI NIH HHS; IK2 BX005301 United States BX BLRD VA; R01 HL161048 United States HL NHLBI NIH HHS; U01 HL163294 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: CD8 T cell; acute lung allograft dysfunction; bronchoalveolar lavage; chronic lung allograft dysfunction; lung transplant; single cell RNA sequencing |
| تواريخ الأحداث: | Date Created: 20240217 Date Completed: 20240601 Latest Revision: 20240710 |
| رمز التحديث: | 20240710 |
| مُعرف محوري في PubMed: | PMC11230518 |
| DOI: | 10.1016/j.healun.2024.02.007 |
| PMID: | 38367738 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1557-3117 |
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| DOI: | 10.1016/j.healun.2024.02.007 |