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Volume 14
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10.3390/ph14050474
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Article

Treatment with an Anti-CX3CL1 Antibody Suppresses M1 Macrophage Infiltration in Interstitial Lung Disease in SKG Mice

by
Satoshi Mizutani
1,
Junko Nishio
1,2,
Kanoh Kondo
1,
Kaori Motomura
1,
Zento Yamada
1,
Shotaro Masuoka
1,
Soichi Yamada
1,
Sei Muraoka
1,
Naoto Ishii
3,
Yoshikazu Kuboi
3,
Sho Sendo
4,
Tetuo Mikami
5,
Toshio Imai
3 and
Toshihiro Nanki
1,*
1
Department of Internal Medicine, Division of Rheumatology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan
2
Department of Immunopathology and Immunoregulation, Toho University School of Medicine, Ota-ku, Tokyo 143-8540, Japan
3
KAN Research Institute, Inc., Chuo-ku, Kobe-shi, Hyogo 650-0047, Japan
4
Department of Internal Medicine, Division of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe-shi, Hyogo 650-0017, Japan
5
Department of Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8540, Japan
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2021, 14(5), 474; https://doi.org/10.3390/ph14050474
Submission received: 6 May 2021 / Accepted: 13 May 2021 / Published: 17 May 2021
(This article belongs to the Special Issue Rheumatic Diseases: Pathophysiology, Targeted Therapy, Focus on Vascular and Pulmonary Manifestations)
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Abstract

CX3C Motif Chemokine Ligand 1 (CX3CL1; fractalkine) has been implicated in the pathogenesis of rheumatoid arthritis (RA) and its inhibition was found to attenuate arthritis in mice as well as in a clinical trial. Therefore, we investigated the effects of an anti-CX3CL1 monoclonal antibody (mAb) on immune-mediated interstitial lung disease (ILD) in SKG mice, which exhibit similar pathological and clinical features to human RA-ILD. CX3CL1 and CX3C chemokine receptor 1 (CX3CR1), the receptor for CX3CL1, were both expressed in the fibroblastic foci of lung tissue and the number of bronchoalveolar fluid (BALF) cells was elevated in ILD in SKG mice. No significant changes were observed in lung fibrosis or the number of BALF cells by the treatment with anti-CX3CL1 mAb. However, significantly greater reductions were observed in the number of M1 macrophages than in M2 macrophages in the BALF of treated mice. Furthermore, CX3CR1 expression levels were significantly higher in M1 macrophages than in M2 macrophages. These results suggest the stronger inhibitory effects of the anti-CX3CL1 mAb treatment against the alveolar infiltration of M1 macrophages than M2 macrophages in ILD in SKG mice. Thus, the CX3CL1-CX3CR1 axis may be involved in the infiltration of inflammatory M1 macrophages in RA-ILD.
Keywords: rheumatoid arthritis; interstitial lung diseases; CX3CL1/fractalkine; CX3CR1; M1 macrophage; M2 macrophage; SKG mice rheumatoid arthritis; interstitial lung diseases; CX3CL1/fractalkine; CX3CR1; M1 macrophage; M2 macrophage; SKG mice

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MDPI and ACS Style

Mizutani, S.; Nishio, J.; Kondo, K.; Motomura, K.; Yamada, Z.; Masuoka, S.; Yamada, S.; Muraoka, S.; Ishii, N.; Kuboi, Y.; et al. Treatment with an Anti-CX3CL1 Antibody Suppresses M1 Macrophage Infiltration in Interstitial Lung Disease in SKG Mice. Pharmaceuticals 2021, 14, 474. https://doi.org/10.3390/ph14050474

AMA Style

Mizutani S, Nishio J, Kondo K, Motomura K, Yamada Z, Masuoka S, Yamada S, Muraoka S, Ishii N, Kuboi Y, et al. Treatment with an Anti-CX3CL1 Antibody Suppresses M1 Macrophage Infiltration in Interstitial Lung Disease in SKG Mice. Pharmaceuticals. 2021; 14(5):474. https://doi.org/10.3390/ph14050474

Chicago/Turabian Style

Mizutani, Satoshi, Junko Nishio, Kanoh Kondo, Kaori Motomura, Zento Yamada, Shotaro Masuoka, Soichi Yamada, Sei Muraoka, Naoto Ishii, Yoshikazu Kuboi, and et al. 2021. "Treatment with an Anti-CX3CL1 Antibody Suppresses M1 Macrophage Infiltration in Interstitial Lung Disease in SKG Mice" Pharmaceuticals 14, no. 5: 474. https://doi.org/10.3390/ph14050474

APA Style

Mizutani, S., Nishio, J., Kondo, K., Motomura, K., Yamada, Z., Masuoka, S., Yamada, S., Muraoka, S., Ishii, N., Kuboi, Y., Sendo, S., Mikami, T., Imai, T., & Nanki, T. (2021). Treatment with an Anti-CX3CL1 Antibody Suppresses M1 Macrophage Infiltration in Interstitial Lung Disease in SKG Mice. Pharmaceuticals, 14(5), 474. https://doi.org/10.3390/ph14050474

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