Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats.
2020
Authors:
Dimitrijević, MirjanaArsenović-Ranin, Nevena
Bufan, Biljana
Nacka-Aleksić, Mirjana
Kosec, Duško
Pilipović, Ivan
Kotur-Stevuljević, Jelena
Simić, Ljubica
Sopta, Jelena
Leposavić, Gordana
Document Type:
Article (Accepted Version)
,
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
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Show full item recordAbstract:
Monocytes' plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to "classical" and "non-classical" monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.
Keywords:
CCR2; CX3CR1; Collagen-induced arthritis; Monocytes’ plasticity; Oxidative stress; Sex differencesSource:
Inflammation, 2020, 43, 2312-2331Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200161 (University of Belgrade, Faculty of Pharmacy) (RS-MESTD-inst-2020-200161)
DOI: 10.1007/s10753-020-01302-0
ISSN: 0360-3997
PubMed: 32857321
WoS: 000563610900001
Scopus: 2-s2.0-85089996658
URI
https://doi.org/10.1007/s10753-020-01302-0http://www.ncbi.nlm.nih.gov/pubmed/32857321
https://radar.ibiss.bg.ac.rs/123456789/3869