Details:

• Alternative Title:
  Int Immunopharmacol
• Personal Author:
  Poole, Jill A. ; Cole, Kathryn E. ; Thiele, Geoffrey M. ; Talmadge, James E. ; England, Bryant R. ; ... More +

  Poole, Jill A. ; Cole, Kathryn E. ; Thiele, Geoffrey M. ; Talmadge, James E. ; England, Bryant R. ; Nelson, Amy J. ; Gleason, Angela ; Schwab, Aaron ; Gaurav, Rohit ; Duryee, Michael J. ; Bailey, Kristina L. ; Romberger, Debra J. ; Hershberger, Daniel ; Graaff, Joel Van De ; May, Sara M. ; Walenz, Rhonda ; Kramer, Bridget ; Mikuls, Ted R. Less -
• 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 identified with intracellular arginase-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 arginase-1 (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.
  
  
• Subjects:
  [+]

  Arthritis, Rheumatoid Humans Idiopathic Pulmonary Fibrosis Lung Diseases, Interstitial Monocytes Myeloid Cells
• Source:
  Int Immunopharmacol. 127:111330
• Pubmed ID:
  38086271
• Pubmed Central ID:
  PMC11503878
• Document Type:
  Journal Article
• Funding:
  I01 BX003635/BX/BLRD VAUnited States/ ; U54 GM115458/GM/NIGMS NIH HHSUnited States/ ; I01 BX004660/BX/BLRD VAUnited States/ ; IK2 CX002203/CX/CSRD VAUnited States/ ; R01 OH012045/OH/NIOSH CDC HHSUnited States/

  I01 BX003635/BX/BLRD VAUnited States/ ; U54 GM115458/GM/NIGMS NIH HHSUnited States/ ; I01 BX004660/BX/BLRD VAUnited States/ ; IK2 CX002203/CX/CSRD VAUnited States/ ; R01 OH012045/OH/NIOSH CDC HHSUnited States/ Less -
• Volume:
  127
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  [+]

  urn:sha-512:cea058cf16bf19e20357e15279ca22fa395948de99dbc5b13e69f5cf355615b380e0d62f343f771b3a70ab12a8c2cf64bcc6be2716a10b2c1f019c7424b09471
• File Type:

• Supporting Files:
  No Additional Files