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Immunotherapy

Anchoring immunosuppression to inflamed tissue

Nature Biomedical Engineering volume 7, pages 1060–1062 (2023)Cite this article

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Fusing the anti-inflammatory enzyme indoleamine 2,3-dioxygenase to the tissue-anchoring protein galectin-3 ameliorates inflammation at the injection site while avoiding systemic immune suppression, as shown in multiple rodent models of inflammation.

Many anti-inflammatory therapeutics injected locally have systemic side effects. Systemic toxicity can be reduced by enhancing the activity of the therapeutics at specific sites or by retaining them locally1. One strategy is to leverage proteins that are abundantly expressed in inflammatory microenvironments. This is the case of galectin-3 (Gal3) — a member of the family of β-galactoside-binding proteins. Gal3 is involved in cell adhesion, migration and immunomodulation via the oligomerization of its N-terminal domain2, and it recognizes β-galactoside-containing glycans via a conserved carbohydrate-recognition domain3. The N terminus of Gal3 can be targeted to disable the protein’s signalling activity (supposedly via the inhibition of oligomerization) without affecting its glycan-binding capacity. By doing so, Gal3–glycan interactions can serve as ‘sweet anchors’ for proteins with relevant biological activity in inflamed tissues: such anchoring sites can favour the local retention of the protein by limiting its diffusion outside of the desired site4.

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Fig. 1: Effects of the IDO–Gal3 fusion protein in rodent models of inflammation.

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Authors and Affiliations

  1. Laboratorio de Glicómica Funcional y Molecular, Programa de Glicociencias, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina

    Karina V. Mariño

  2. Laboratorio de Glicomedicina, Programa de Glicociencias, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina

    Ada G. Blidner & Gabriel A. Rabinovich

  3. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    Gabriel A. Rabinovich

Authors
  1. Karina V. Mariño
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  2. Ada G. Blidner
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  3. Gabriel A. Rabinovich
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Correspondence to Gabriel A. Rabinovich.

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The authors declare no competing interests.

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Mariño, K.V., Blidner, A.G. & Rabinovich, G.A. Anchoring immunosuppression to inflamed tissue. Nat. Biomed. Eng 7, 1060–1062 (2023). https://doi.org/10.1038/s41551-023-01055-9

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