Expansion of Distinct Peripheral Blood Myeloid Cell Subpopulations in Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease

Details

• Personal Author:
  Bailey KL ; Cole KE ; Duryee MJ ; England BR ; Gaurav R ; Gleason A ; Hershberger D ; Kramer B ; May SM ; Mikuls TR ; Nelson AJ ; Poole JA ; Romberger DJ ; Schwab A ; Talmadge JE ; Thiele GM ; Van De Graaff J ; Walenz R
• Description:
  Objectives: Interstitial lung disease (ILD) is associated with significant mortality in rheumatoid arthritis (RA) patients with key cellular players remaining largely unknown. This study aimed to characterize inflammatory and myeloid derived suppressor cell (MDSC) subpopulations in RA-ILD as compared to RA, idiopathic pulmonary fibrosis (IPF) without autoimmunity, and controls. Methods: Peripheral blood was collected from patients with RA, RA-ILD, IPF, and controls (N = 60, 15/cohort). Myeloid cell subpopulations were identified phenotypically by flow cytometry using the following markers:CD45,CD3,CD19,CD56,CD11b,HLA-DR,CD14,CD16,CD15,CD125,CD33. Functionality of subsets were identified with intracellular arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression. Results: There was increased intermediate (CD14++CD16+) and nonclassical (CD14+/-CD16++) and decreased classical (CD14++CD16-) monocytes in RA, RA-ILD, and IPF vs. control. Intermediate monocytes were higher and classical monocytes were lower in RA-ILD vs. RA but not IPF. Monocytic (m)MDSCs were higher in RA-ILD vs. control and RA but not IPF. Granulocytic (g)MDSCs did not significantly differ. In contrast, neutrophils were increased in IPF and RA-ILD patients with elevated expression of Arg-1 sharing similar dimensional clustering pattern. Eosinophils were increased in RA-ILD vs. controls, RA and IPF. Across cohorts, iNOS was decreased in intermediate/nonclassical monocytes but increased in mMDSCs vs. classical monocytes. In RA-ILD, iNOS positive mMDSCs were increased versus classic monocytes. Conclusions: Myeloid cell subpopulations are significantly modulated in RA-ILD patients with expansion of CD16+ monocytes, mMDSCs, and neutrophils, a phenotypic profile more aligned with IPF than other RA patients. Eosinophil expansion was unique to RA-ILD, potentially facilitating disease pathogenesis and providing a future therapeutic target. [Description provided by NIOSH]
• Subjects:
  Biomarkers Immune System Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Biomarker Autoimmune Diseases Eosinophil Gene Expression Immune Reaction Interstitial Lung Disease Lung Disease MDSC Monocyte Myeloid Tissue Neutrophil Pulmonary Fibrosis Rheumatoid Arthritis Rheumatoid Disorders

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• ISSN:
  1567-5769
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  127
• NIOSHTIC Number:
  nn:20069029
• Citation:
  Int Immunopharmacol 2024 Jan; 127:111330
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center
• Peer Reviewed:
  True
• Start Date:
  20210901
• Source Full Name:
  International Immunopharmacology
• End Date:
  20250831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a2f5cf79a854eaeecc81039cde5611823e8d5b397e4e75790c1e323680322b225865d7f5392c064f36b4f3f36c92e4c7b640add3b090655927d56f6af0a63077
• Download URL:
  https://stacks.cdc.gov/view/cdc/207579/cdc_207579_DS1.pdf
• File Type:
  [PDF - 5.23 MB ]