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The ratio of CD163-positive macrophages to Iba1-positive macrophages is low in the intima in the early stage of cutaneous arteritis

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Abstract

The etiology of polyarteritis nodosa (PAN) and localized PAN, including cutaneous arteritis (CA), remains unknown; however, initial endothelial damage has been implicated. The intima of the vasculitis lesions is predominantly infiltrated by innate-like bystander-activated CD8 T cells, in addition to the macrophages. Macrophages are among the major inflammatory cells involved in innate immunity and are classified into M1 and M2 subtypes. M1-type macrophages kill pathogens and cause inflammation, while M2-type macrophages promote the repair of tissues. Macrophage subtypes infiltrating in PAN and localized PAN vasculitis lesions have not yet been investigated. Innate immune response to a triggering factor on the endothelial cell surface may initiate CA pathogenesis. Thus, many M1-type macrophages may infiltrate in the intima during early CA. We assessed this hypothesis by immunohistochemical observation of macrophage phenotypes and polarization. Twenty-seven skin biopsy specimens from patients with CA were retrieved. Based on histology, we classified CA into four phases. The phenotypes of infiltrating macrophages in CA were evaluated by immunohistochemistry using antibodies against Iba-1, a pan-macrophage marker, and CD163, an M2-type macrophage marker. Our results showed that the ratio of CD163-positive M2-type macrophages to Iba1-positive macrophages was lower in the intima in the early stage of CA than in the later stage. In the media to adventitia, there was no significant difference in the ratios between these stages. These findings indicate that innate immunity is involved in the intima in the early stage of CA, suggesting that a trigger for CA might exist in endothelial cells.

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Acknowledgments

The authors thank Ms. Tomoko Nishizawa and Ms. Shizu Fujii for their technical assistance.

Funding

This research was partially supported by a grant from JSPS KAKENHI [Grant Number JP 18 K15077 to MK].

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Authors and Affiliations

  1. Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Mikiko Kobayashi, Yuki Matsumoto, Hidetoshi Satomi, Ayako Tateishi, Maki Ohya & Hiroyuki Kanno

  2. Department of Pathology, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano, 380-8582, Japan

    Hidetoshi Satomi & Ichiro Ito

Authors
  1. Mikiko Kobayashi
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  2. Yuki Matsumoto
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  3. Hidetoshi Satomi
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  4. Ayako Tateishi
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  5. Maki Ohya
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  6. Ichiro Ito
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  7. Hiroyuki Kanno
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by Mikiko Kobayashi, Yuki Matsumoto, and Hidetoshi Satomi. Data collection and analysis were performed by Mikiko Kobayashi, Maki Ohya, and Ayako Tateishi. Ichiro Ito and Hiroyuki Kanno assisted with data analysis and interpretation. The first draft of the manuscript was written by Mikiko Kobayashi, and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mikiko Kobayashi.

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This study was approved by the ethics committee of Shinshu University School of Medicine, Japan (No. 3136).

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The authors declare that they have no conflict of interest.

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Kobayashi, M., Matsumoto, Y., Satomi, H. et al. The ratio of CD163-positive macrophages to Iba1-positive macrophages is low in the intima in the early stage of cutaneous arteritis. Immunol Res 68, 152–160 (2020). https://doi.org/10.1007/s12026-020-09140-w

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