Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease

Jill A. Poole; Kathryn E. Cole; Geoffrey M. Thiele; James E. Talmadge; Bryant R. England; Amy J. Nelson; Angela Gleason; Aaron Schwab; Rohit Gaurav; Michael J. Duryee; Kristina L. Bailey; Debra J. Romberger; Daniel Hershberger; Joel Van De Graaff; Sara M. May; Rhonda Walenz; Bridget Kramer; Ted R. Mikuls

doi:10.1016/j.intimp.2023.111330

Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease

Jill A. Poole, Kathryn E. Cole, Geoffrey M. Thiele, James E. Talmadge, Bryant R. England, Amy J. Nelson, Angela Gleason, Aaron Schwab, Rohit Gaurav, Michael J. Duryee, Kristina L. Bailey, Debra J. Romberger, Daniel Hershberger, Joel Van De Graaff, Sara M. May, Rhonda Walenz, Bridget Kramer, Ted R. Mikuls

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	111330
Journal	International Immunopharmacology
Volume	127
DOIs	https://doi.org/10.1016/j.intimp.2023.111330
State	Published - Jan 25 2024

Keywords

Biomarker
Eosinophil
Interstitial lung disease
MDSC
Monocyte
Neutrophil
Pulmonary fibrosis
Rheumatoid arthritis

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Pharmacology

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10.1016/j.intimp.2023.111330

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Poole, J. A., Cole, K. E., Thiele, G. M., Talmadge, J. E., England, B. R., Nelson, A. J., Gleason, A., Schwab, A., Gaurav, R., Duryee, M. J., Bailey, K. L., Romberger, D. J., Hershberger, D., De Graaff, J. V., May, S. M., Walenz, R., Kramer, B., & Mikuls, T. R. (2024). Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease. International Immunopharmacology, 127, Article 111330. https://doi.org/10.1016/j.intimp.2023.111330

Poole, JA, Cole, KE, Thiele, GM, Talmadge, JE, England, BR, Nelson, AJ, Gleason, A, Schwab, A, Gaurav, R, Duryee, MJ , Bailey, KL , Romberger, DJ, Hershberger, D, De Graaff, JV, May, SM, Walenz, R, Kramer, B & Mikuls, TR 2024, 'Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease', International Immunopharmacology, vol. 127, 111330. https://doi.org/10.1016/j.intimp.2023.111330

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title = "Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease",

abstract = "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.",

keywords = "Biomarker, Eosinophil, Interstitial lung disease, MDSC, Monocyte, Neutrophil, Pulmonary fibrosis, Rheumatoid arthritis",

author = "Poole, {Jill A.} and Cole, {Kathryn E.} and Thiele, {Geoffrey M.} and Talmadge, {James E.} and England, {Bryant R.} and Nelson, {Amy J.} and Angela Gleason and Aaron Schwab and Rohit Gaurav and Duryee, {Michael J.} and Bailey, {Kristina L.} and Romberger, {Debra J.} and Daniel Hershberger and {De Graaff}, {Joel Van} and May, {Sara M.} and Rhonda Walenz and Bridget Kramer and Mikuls, {Ted R.}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

year = "2024",

month = jan,

day = "25",

doi = "10.1016/j.intimp.2023.111330",

language = "English (US)",

volume = "127",

journal = "International Immunopharmacology",

issn = "1567-5769",

publisher = "Elsevier",

}

TY - JOUR

T1 - Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease

AU - Poole, Jill A.

AU - Cole, Kathryn E.

AU - Thiele, Geoffrey M.

AU - Talmadge, James E.

AU - England, Bryant R.

AU - Nelson, Amy J.

AU - Gleason, Angela

AU - Schwab, Aaron

AU - Gaurav, Rohit

AU - Duryee, Michael J.

AU - Bailey, Kristina L.

AU - Romberger, Debra J.

AU - Hershberger, Daniel

AU - De Graaff, Joel Van

AU - May, Sara M.

AU - Walenz, Rhonda

AU - Kramer, Bridget

AU - Mikuls, Ted R.

PY - 2024/1/25

Y1 - 2024/1/25

N2 - 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.

AB - 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.

KW - Biomarker

KW - Eosinophil

KW - Interstitial lung disease

KW - MDSC

KW - Monocyte

KW - Neutrophil

KW - Pulmonary fibrosis

KW - Rheumatoid arthritis

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U2 - 10.1016/j.intimp.2023.111330

DO - 10.1016/j.intimp.2023.111330

M3 - Article

C2 - 38086271

AN - SCOPUS:85179604995

SN - 1567-5769

VL - 127

JO - International Immunopharmacology

JF - International Immunopharmacology

M1 - 111330

ER -

Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease

Abstract

Keywords

ASJC Scopus subject areas

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