Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses

Rie Suematsu, Tomofumi Miyamoto, Shinobu Saijo, Sho Yamasaki, Yoshifumi Tada, Hiroki Yoshida, Yasunobu Miyake

研究成果: ジャーナルへの寄稿記事

抄録

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of cell-surface immune receptors that bind to sialic acid at terminal glycan residues. Siglecs also recognize nonsialic acid ligands, many of which remain to be characterized. Here, we found that Siglec5 and Siglec14 recognize lipid compounds produced by Trichophyton, a fungal genus containing several pathogenic species. Biochemical approaches revealed that the Siglec ligands are fungal alkanes and triacylglycerols, an unexpected finding that prompted us to search for endogenous lipid ligands of Siglecs. Siglec5 weakly recognized several endogenous lipids, but the mitochondrial lipid cardiolipin and the anti-inflammatory lipid 5-palmitic acid-hydroxystearic acid exhibited potent ligand activity on Siglec5. Further, the hydrophobic stretch in the Siglec5 N terminus region was found to be required for efficient recognition of these lipids. Notably, this hydrophobic stretch was dispensable for recognition of sialic acid. Siglec5 inhibited cell activation upon ligand binding, and accordingly, the lipophilic ligands suppressed interleukin-8 (IL-8) production in Siglec5-expressing human monocytic cells. Siglec14 and Siglec5 have high sequence identity in the extracellular region, and Siglec14 also recognized the endogenous lipids. However, unlike Siglec5, Siglec14 transduces activating signals upon ligand recognition. Indeed, the endogenous lipids induced IL-8 production in Siglec14-expressing human monocytic cells. These results indicatedthat Siglec5 and Siglec14 can recognize lipophilic ligands that thereby modulate innate immune responses. To our knowledge, this is the first study reporting the binding of Siglecs to lipid ligands, expanding our understanding of the biological function and importance of Siglecs in the innate immunity.

元の言語英語
ページ(範囲)16776-16788
ページ数13
ジャーナルJournal of Biological Chemistry
294
発行部数45
DOI
出版物ステータス出版済み - 1 1 2019

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Sialic Acid Binding Immunoglobulin-like Lectins
Innate Immunity
Ligands
Lipids
N-Acetylneuraminic Acid
Interleukin-8
Trichophyton
Cardiolipins
Alkanes
Acids
Palmitic Acid
Cell Surface Receptors
Polysaccharides
Triglycerides
Anti-Inflammatory Agents
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses. / Suematsu, Rie; Miyamoto, Tomofumi; Saijo, Shinobu; Yamasaki, Sho; Tada, Yoshifumi; Yoshida, Hiroki; Miyake, Yasunobu.

:: Journal of Biological Chemistry, 巻 294, 番号 45, 01.01.2019, p. 16776-16788.

研究成果: ジャーナルへの寄稿記事

Suematsu, R, Miyamoto, T, Saijo, S, Yamasaki, S, Tada, Y, Yoshida, H & Miyake, Y 2019, 'Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses', Journal of Biological Chemistry, 巻. 294, 番号 45, pp. 16776-16788. https://doi.org/10.1074/jbc.RA119.009835
Suematsu, Rie ; Miyamoto, Tomofumi ; Saijo, Shinobu ; Yamasaki, Sho ; Tada, Yoshifumi ; Yoshida, Hiroki ; Miyake, Yasunobu. / Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses. :: Journal of Biological Chemistry. 2019 ; 巻 294, 番号 45. pp. 16776-16788.
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abstract = "Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of cell-surface immune receptors that bind to sialic acid at terminal glycan residues. Siglecs also recognize nonsialic acid ligands, many of which remain to be characterized. Here, we found that Siglec5 and Siglec14 recognize lipid compounds produced by Trichophyton, a fungal genus containing several pathogenic species. Biochemical approaches revealed that the Siglec ligands are fungal alkanes and triacylglycerols, an unexpected finding that prompted us to search for endogenous lipid ligands of Siglecs. Siglec5 weakly recognized several endogenous lipids, but the mitochondrial lipid cardiolipin and the anti-inflammatory lipid 5-palmitic acid-hydroxystearic acid exhibited potent ligand activity on Siglec5. Further, the hydrophobic stretch in the Siglec5 N terminus region was found to be required for efficient recognition of these lipids. Notably, this hydrophobic stretch was dispensable for recognition of sialic acid. Siglec5 inhibited cell activation upon ligand binding, and accordingly, the lipophilic ligands suppressed interleukin-8 (IL-8) production in Siglec5-expressing human monocytic cells. Siglec14 and Siglec5 have high sequence identity in the extracellular region, and Siglec14 also recognized the endogenous lipids. However, unlike Siglec5, Siglec14 transduces activating signals upon ligand recognition. Indeed, the endogenous lipids induced IL-8 production in Siglec14-expressing human monocytic cells. These results indicatedthat Siglec5 and Siglec14 can recognize lipophilic ligands that thereby modulate innate immune responses. To our knowledge, this is the first study reporting the binding of Siglecs to lipid ligands, expanding our understanding of the biological function and importance of Siglecs in the innate immunity.",
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AU - Suematsu, Rie

AU - Miyamoto, Tomofumi

AU - Saijo, Shinobu

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AU - Yoshida, Hiroki

AU - Miyake, Yasunobu

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AB - Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of cell-surface immune receptors that bind to sialic acid at terminal glycan residues. Siglecs also recognize nonsialic acid ligands, many of which remain to be characterized. Here, we found that Siglec5 and Siglec14 recognize lipid compounds produced by Trichophyton, a fungal genus containing several pathogenic species. Biochemical approaches revealed that the Siglec ligands are fungal alkanes and triacylglycerols, an unexpected finding that prompted us to search for endogenous lipid ligands of Siglecs. Siglec5 weakly recognized several endogenous lipids, but the mitochondrial lipid cardiolipin and the anti-inflammatory lipid 5-palmitic acid-hydroxystearic acid exhibited potent ligand activity on Siglec5. Further, the hydrophobic stretch in the Siglec5 N terminus region was found to be required for efficient recognition of these lipids. Notably, this hydrophobic stretch was dispensable for recognition of sialic acid. Siglec5 inhibited cell activation upon ligand binding, and accordingly, the lipophilic ligands suppressed interleukin-8 (IL-8) production in Siglec5-expressing human monocytic cells. Siglec14 and Siglec5 have high sequence identity in the extracellular region, and Siglec14 also recognized the endogenous lipids. However, unlike Siglec5, Siglec14 transduces activating signals upon ligand recognition. Indeed, the endogenous lipids induced IL-8 production in Siglec14-expressing human monocytic cells. These results indicatedthat Siglec5 and Siglec14 can recognize lipophilic ligands that thereby modulate innate immune responses. To our knowledge, this is the first study reporting the binding of Siglecs to lipid ligands, expanding our understanding of the biological function and importance of Siglecs in the innate immunity.

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