Activation of CD8 + T Cells in Chronic Obstructive Pulmonary Disease Lung.

Autor:	Villaseñor-Altamirano AB; Division of Pulmonary and Critical Care Medicine.; Harvard Medical School, Boston, Massachusetts., Jain D; Pulmonary Drug Discovery Laboratory, Pharmaceuticals Research and Development, Bayer US LLC, Boston, Massachusetts; and., Jeong Y; Division of Pulmonary and Critical Care Medicine.; Harvard Medical School, Boston, Massachusetts., Menon JA; Division of Pulmonary and Critical Care Medicine., Kamiya M; Division of Pulmonary and Critical Care Medicine.; Harvard Medical School, Boston, Massachusetts., Haider H; Division of Pulmonary and Critical Care Medicine., Manandhar R; Division of Pulmonary and Critical Care Medicine., Sheikh MDA; Division of Pulmonary and Critical Care Medicine., Athar H; Division of Pulmonary and Critical Care Medicine.; Pulmonary Drug Discovery Laboratory, Pharmaceuticals Research and Development, Bayer US LLC, Boston, Massachusetts; and., Merriam LT; Division of Pulmonary and Critical Care Medicine., Ryu MH; Channing Division of Network Medicine, and.; Harvard Medical School, Boston, Massachusetts., Sasaki T; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, and.; Harvard Medical School, Boston, Massachusetts., Castaldi PJ; Channing Division of Network Medicine, and.; Harvard Medical School, Boston, Massachusetts., Rao DA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, and.; Harvard Medical School, Boston, Massachusetts., Sholl LM; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Vivero M; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Hersh CP; Channing Division of Network Medicine, and.; Harvard Medical School, Boston, Massachusetts., Zhou X; Channing Division of Network Medicine, and.; Harvard Medical School, Boston, Massachusetts., Veerkamp J; Pharmaceuticals, Research & Early Development Precision Medicine RED (preMED), Pharmaceuticals Research and Development, Bayer AG, Wuppertal, Germany., Yun JH; Channing Division of Network Medicine, and.; Harvard Medical School, Boston, Massachusetts., Kim EY; Division of Pulmonary and Critical Care Medicine.; Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2023 Dec 01; Vol. 208 (11), pp. 1177-1195.
DOI:	10.1164/rccm.202305-0924OC
Abstrakt:	Rationale: Despite the importance of inflammation in chronic obstructive pulmonary disease (COPD), the immune cell landscape in the lung tissue of patients with mild-moderate disease has not been well characterized at the single-cell and molecular level. Objectives: To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution. Methods: We performed single-cell transcriptomic, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD ( n  = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction ( n  = 5), end-stage COPD ( n  = 2), control ( n  = 6), or donors ( n  = 4). We validated in an independent patient cohort ( N  = 929) and integrated with the Hhip +/- murine model of COPD. Measurements and Main Results: Mild-moderate COPD lungs have increased abundance of two CD8 +  T cell subpopulations: cytotoxic KLRG1 + TIGIT + CX3CR1 +  TEMRA (T effector memory CD45RA + ) cells, and DNAM-1 + CCR5 +  T resident memory (T RM ) cells. These CD8 +  T cells interact with myeloid and alveolar type II cells via IFNG and have hyperexpanded T-cell receptor clonotypes. In an independent cohort, the CD8 + KLRG1 + TEMRA cells are increased in mild-moderate COPD lung compared with control or end-stage COPD lung. Human CD8 + KLRG1 +  TEMRA cells are similar to CD8 +  T cells driving inflammation in an aging-related murine model of COPD. Conclusions: CD8 +  TEMRA cells are increased in mild-moderate COPD lung and may contribute to inflammation that precedes severe disease. Further study of these CD8 +  T cells may have therapeutic implications for preventing severe COPD.
Databáze:	MEDLINE
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