AUTHOR=Fukui Shoichi , Iwamoto Naoki , Takatani Ayuko , Igawa Takashi , Shimizu Toshimasa , Umeda Masataka , Nishino Ayako , Horai Yoshiro , Hirai Yasuko , Koga Tomohiro , Kawashiri Shin-ya , Tamai Mami , Ichinose Kunihiro , Nakamura Hideki , Origuchi Tomoki , Masuyama Ritsuko , Kosai Kosuke , Yanagihara Katsunori , Kawakami Atsushi 

TITLE=M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01958

DOI=10.3389/fimmu.2017.01958

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Objectives</title><p>We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC) differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA).</p></sec><sec id="ST2"><title>Methods</title><p>Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation <italic>in vitro</italic>.</p></sec><sec id="ST3"><title>Results</title><p>Forty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were anticitrullinated protein antibody (ACPA) positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number <italic>in vitro</italic> in RA patients (ρ = 0.81, <italic>p</italic> &lt; 0.001). The ACPA-positive patients had significantly higher M1/M2 ratios <italic>in vivo</italic> (<italic>p</italic> = 0.028) and significantly greater numbers of OCs <italic>in vitro</italic> (<italic>p</italic> = 0.005) than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to <italic>in vitro</italic> osteoclastogenesis. RA patients with M1/M2 ratios &gt;1 (having relatively more M1 monocytes) had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes <italic>in vitro</italic> produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.</p></sec><sec id="ST4"><title>Conclusion</title><p>M1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.</p></sec>