Laurel A Monticelli1,2, Joshua M Diamond3, Steven A Saenz2, Elia D Tait Wojno2, Mary K Porteous3, Edward Cantu4, David Artis2, Jason D Christie3. 1. Division of Pulmonary and Critical Care Medicine and. 2. Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, New York; and. 3. Division of Pulmonary, Allergy, and Critical Care Medicine, and. 4. Division of Cardiovascular Surgery, Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation, but the immunologic mechanisms are poorly understood. Innate lymphoid cells (ILC) are a heterogeneous family of immune cells regulating pathologic inflammation and beneficial tissue repair. However, whether changes in donor-derived lung ILC populations are associated with PGD development has never been examined. Objectives: To determine whether PGD in chronic obstructive pulmonary disease or interstitial lung disease transplant recipients is associated with alterations in ILC subset composition within the allograft. Methods: We performed a single-center cohort study of lung transplantation patients with surgical biopsies of donor tissue taken before, and immediately after, allograft reperfusion. Donor immune cells from 18 patients were characterized phenotypically by flow cytometry for single-cell resolution of distinct ILC subsets. Changes in the percentage of ILC subsets with reperfusion or PGD (grade 3 within 72 h) were assessed.Measurements and Main Results: Allograft reperfusion resulted in significantly decreased frequencies of natural killer cells and a trend toward reduced ILC populations, regardless of diagnosis (interstitial lung disease or chronic obstructive pulmonary disease). Seven patients developed PGD (38.9%), and PGD development was associated with selective reduction of the ILC2 subset after reperfusion. Conversely, patients without PGD exhibited significantly higher ILC1 frequencies before reperfusion, accompanied by elevated ILC2 frequencies after allograft reperfusion.Conclusions: The composition of donor ILC subsets is altered after allograft reperfusion and is associated with PGD development, suggesting that ILCs may be involved in regulating lung injury in lung transplant recipients.
Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation, but the immunologic mechanisms are poorly understood. Innate lymphoid cells (ILC) are a heterogeneous family of immune cells regulating pathologic inflammation and beneficial tissue repair. However, whether changes in donor-derived lung ILC populations are associated with PGD development has never been examined. Objectives: To determine whether PGD in chronic obstructive pulmonary disease or interstitial lung disease transplant recipients is associated with alterations in ILC subset composition within the allograft. Methods: We performed a single-center cohort study of lung transplantation patients with surgical biopsies of donor tissue taken before, and immediately after, allograft reperfusion. Donor immune cells from 18 patients were characterized phenotypically by flow cytometry for single-cell resolution of distinct ILC subsets. Changes in the percentage of ILC subsets with reperfusion or PGD (grade 3 within 72 h) were assessed.Measurements and Main Results: Allograft reperfusion resulted in significantly decreased frequencies of natural killer cells and a trend toward reduced ILC populations, regardless of diagnosis (interstitial lung disease or chronic obstructive pulmonary disease). Seven patients developed PGD (38.9%), and PGD development was associated with selective reduction of the ILC2 subset after reperfusion. Conversely, patients without PGD exhibited significantly higher ILC1 frequencies before reperfusion, accompanied by elevated ILC2 frequencies after allograft reperfusion.Conclusions: The composition of donor ILC subsets is altered after allograft reperfusion and is associated with PGD development, suggesting that ILCs may be involved in regulating lung injury in lung transplant recipients.
Authors: Jillian L Barlow; Agustin Bellosi; Clare S Hardman; Lesley F Drynan; See Heng Wong; James P Cruickshank; Andrew N J McKenzie Journal: J Allergy Clin Immunol Date: 2011-11-12 Impact factor: 10.793
Authors: Joshua M Diamond; Selim Arcasoy; Cassie C Kennedy; Michael Eberlein; Jonathan P Singer; Glenda M Patterson; Jeffrey D Edelman; Gundeep Dhillon; Tahuanty Pena; Steven M Kawut; James C Lee; Reda Girgis; John Dark; Gabriel Thabut Journal: J Heart Lung Transplant Date: 2017-07-26 Impact factor: 10.247
Authors: Jenny M Mjösberg; Sara Trifari; Natasha K Crellin; Charlotte P Peters; Cornelis M van Drunen; Berber Piet; Wytske J Fokkens; Tom Cupedo; Hergen Spits Journal: Nat Immunol Date: 2011-09-11 Impact factor: 25.606
Authors: Jochem H Bernink; Charlotte P Peters; Marius Munneke; Anje A te Velde; Sybren L Meijer; Kees Weijer; Hulda S Hreggvidsdottir; Sigrid E Heinsbroek; Nicolas Legrand; Christianne J Buskens; Willem A Bemelman; Jenny M Mjösberg; Hergen Spits Journal: Nat Immunol Date: 2013-01-20 Impact factor: 25.606
Authors: Joshua M Diamond; James C Lee; Steven M Kawut; Rupal J Shah; A Russell Localio; Scarlett L Bellamy; David J Lederer; Edward Cantu; Benjamin A Kohl; Vibha N Lama; Sangeeta M Bhorade; Maria Crespo; Ejigayehu Demissie; Joshua Sonett; Keith Wille; Jonathan Orens; Ashish S Shah; Ann Weinacker; Selim Arcasoy; Pali D Shah; David S Wilkes; Lorraine B Ware; Scott M Palmer; Jason D Christie Journal: Am J Respir Crit Care Med Date: 2013-01-10 Impact factor: 21.405
Authors: Zequan Yang; Ashish K Sharma; Joel Linden; Irving L Kron; Victor E Laubach Journal: J Thorac Cardiovasc Surg Date: 2009-03 Impact factor: 5.209
Authors: Yannick Simoni; Michael Fehlings; Henrik N Kløverpris; Naomi McGovern; Si-Lin Koo; Chiew Yee Loh; Shawn Lim; Ayako Kurioka; Joannah R Fergusson; Choong-Leong Tang; Ming Hian Kam; Koh Dennis; Tony Kiat Hon Lim; Alexander Chung Yaw Fui; Chan Weng Hoong; Jerry Kok Yen Chan; Maria Curotto de Lafaille; Sriram Narayanan; Sonia Baig; Muhammad Shabeer; Sue-Anne Ee Shiow Toh; Henry Kun Kiaang Tan; Rosslyn Anicete; Eng-Huat Tan; Angela Takano; Paul Klenerman; Alasdair Leslie; Daniel S W Tan; Iain Beehuat Tan; Florent Ginhoux; Evan W Newell Journal: Immunity Date: 2016-12-13 Impact factor: 43.474
Authors: Niels P van der Kaaij; Jolanda Kluin; Jack J Haitsma; Michael A den Bakker; Bart N Lambrecht; Burkhard Lachmann; Ron W F de Bruin; Ad J J C Bogers Journal: Respir Res Date: 2008-03-26
Authors: Jaideep Dhariwal; Aoife Cameron; Ernie Wong; Malte Paulsen; Maria-Belen Trujillo-Torralbo; Ajerico Del Rosario; Eteri Bakhsoliani; Tatiana Kebadze; Mark Almond; Hugo Farne; Leila Gogsadze; Julia Aniscenko; Batika M J Rana; Trevor T Hansel; David J Jackson; Onn Min Kon; Michael R Edwards; Roberto Solari; David J Cousins; Ross P Walton; Sebastian L Johnston Journal: Am J Respir Crit Care Med Date: 2021-12-01 Impact factor: 30.528
Authors: Yizhan Guo; Zhongcheng Mei; Dongge Li; Anirban Banerjee; May A Khalil; Allen Burke; Jon Ritter; Christine Lau; Daniel Kreisel; Andrew E Gelman; Elizabeth Jacobsen; Irina G Luzina; Sergei P Atamas; Alexander Sasha Krupnick Journal: Am J Transplant Date: 2022-05-17 Impact factor: 9.369
Authors: Daniel R Calabrese; Emily Aminian; Benat Mallavia; Fengchun Liu; Simon J Cleary; Oscar A Aguilar; Ping Wang; Jonathan P Singer; Steven R Hays; Jeffrey A Golden; Jasleen Kukreja; Daniel Dugger; Mary Nakamura; Lewis L Lanier; Mark R Looney; John R Greenland Journal: J Clin Invest Date: 2021-02-01 Impact factor: 14.808
Authors: Andy Chao Hsuan Lee; Arianna Edobor; Thirushan Wigakumar; Maria Lysandrou; Laura K Johnston; Phillip McMullen; Vikranth Mirle; Ashley Diaz; Ryan Piech; Rebecca Rose; Martin Jendrisak; Diego di Sabato; Kumaran Shanmugarajah; John Fung; Jessica Donington; Maria Lucia Madariaga Journal: Clin Transplant Date: 2022-04-18 Impact factor: 3.456