2. Academic Validation
  3. Neutrophil S100A9 supports M2 macrophage niche formation in granulomas

Neutrophil S100A9 supports M2 macrophage niche formation in granulomas

  • iScience. 2023 Jan 31;26(3):106081. doi: 10.1016/j.isci.2023.106081.
Tatsuaki Mizutani 1 2,  Toshiaki Ano 1 2,  Yuya Yoshioka 1 2,  Satoshi Mizuta 3,  Keiko Takemoto 4,  Yuki Ouchi 1 2,  Daisuke Morita 1 2,  Satsuki Kitano 5,  Hitoshi Miyachi 5,  Tatsuaki Tsuruyama 6,  Nagatoshi Fujiwara 7,  Masahiko Sugita 1 2
Affiliations

Affiliations

  • 1 Laboratory of Cell Regulation, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • 2 Laboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
  • 3 Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
  • 4 Laboratory of Immune Regulation, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • 5 Reproductive Engineering Team, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • 6 Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 7 Department of Food and Nutrition, Tezukayama University, Nara, Japan.
PMID: 36843852 DOI: 10.1016/j.isci.2023.106081
Abstract

Mycobacterium Infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the COX-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Because the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 Inhibitor, we propose the S100A9/COX-2 axis as a major pathway driving M2 niche formation in granulomas.

Keywords

Cancer; Components of the immune system; Immunology; Molecular biology.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10528
    99.70%, S100A9 Inhibitor