TY - JOUR
T1 - GM-CSF drives IL-6 production by macrophages in polymyalgia rheumatica
AU - Jiemy, William F
AU - Zhang, Anqi
AU - Abdulahad, Wayel H
AU - Reitsema, Rosanne D
AU - van Sleen, Yannick
AU - Sandovici, Maria
AU - Alegria, Guillermo Carvajal
AU - Cornec, Divi
AU - Devauchelle-Pensec, Valérie
AU - Hemon, Patrice
AU - Quéré, Baptiste
AU - Boukhlal, Sara
AU - Roozendaal, Caroline
AU - Kwee, Thomas Christian
AU - Dasgupta, Bhaskar
AU - Diepstra, Arjan
AU - Heeringa, Peter
AU - Brouwer, Elisabeth
AU - van der Geest, Kornelis S M
N1 - Copyright © 2025. Published by Elsevier B.V.
PY - 2025/2/5
Y1 - 2025/2/5
N2 - OBJECTIVES: Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR.METHODS: Monocyte phenotypes were investigated by flow cytometry in peripheral blood (PMR, n = 22; healthy controls, n = 20) and paired subacromial-subdeltoid (SASD) bursal fluid (PMR, n = 9). Macrophages in SASD bursa were characterised by immunohistochemistry and immunofluorescence (PMR, n = 12; controls undergoing shoulder replacement surgery, n = 10). The functions of cytokines expressed in PMR-affected tissue were examined using macrophage differentiation cultures (PMR, n = 7; healthy controls, n = 7).RESULTS: Monocytes (CD14
highCD16
- and CD14
highCD16
+) were increased in blood of PMR patients and activated in bursal fluid. Macrophages dominated immune infiltrates in PMR-affected tissue, expressing various proinflammatory cytokines. While interleukin (IL)-6 and interferon-gamma (IFN-γ) expression was abundant in both PMR and control tissue, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) were significantly increased in PMR tissue. Macrophages in PMR-affected tissue showed an elevated CD206/folate receptor β ratio, reflecting a GM-CSF skewed signature. A combination of GM-CSF/M-CSF/IFN-γ significantly boosted IL-6 production in vitro, while limited IL-6 production was observed without GM-CSF.
CONCLUSIONS: The monocyte compartment is expanded and activated in PMR. Macrophages in PMR-affected tissue produce abundant proinflammatory cytokines such as IL-6. A network of locally expressed cytokines, including GM-CSF, M-CSF, and IFN-γ, may drive the proinflammatory functions of these macrophages. Overall, macrophages may constitute key therapeutic targets for PMR.
AB - OBJECTIVES: Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR.METHODS: Monocyte phenotypes were investigated by flow cytometry in peripheral blood (PMR, n = 22; healthy controls, n = 20) and paired subacromial-subdeltoid (SASD) bursal fluid (PMR, n = 9). Macrophages in SASD bursa were characterised by immunohistochemistry and immunofluorescence (PMR, n = 12; controls undergoing shoulder replacement surgery, n = 10). The functions of cytokines expressed in PMR-affected tissue were examined using macrophage differentiation cultures (PMR, n = 7; healthy controls, n = 7).RESULTS: Monocytes (CD14
highCD16
- and CD14
highCD16
+) were increased in blood of PMR patients and activated in bursal fluid. Macrophages dominated immune infiltrates in PMR-affected tissue, expressing various proinflammatory cytokines. While interleukin (IL)-6 and interferon-gamma (IFN-γ) expression was abundant in both PMR and control tissue, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) were significantly increased in PMR tissue. Macrophages in PMR-affected tissue showed an elevated CD206/folate receptor β ratio, reflecting a GM-CSF skewed signature. A combination of GM-CSF/M-CSF/IFN-γ significantly boosted IL-6 production in vitro, while limited IL-6 production was observed without GM-CSF.
CONCLUSIONS: The monocyte compartment is expanded and activated in PMR. Macrophages in PMR-affected tissue produce abundant proinflammatory cytokines such as IL-6. A network of locally expressed cytokines, including GM-CSF, M-CSF, and IFN-γ, may drive the proinflammatory functions of these macrophages. Overall, macrophages may constitute key therapeutic targets for PMR.
U2 - 10.1016/j.ard.2025.01.004
DO - 10.1016/j.ard.2025.01.004
M3 - Article
C2 - 39915203
SN - 0003-4967
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
ER -