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Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease

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Abstract

Toll-interacting protein (TOLLIP) is a ubiquitous intracellular adaptor protein involved in multiple intracellular signaling pathways. It plays a key role in mediating inflammatory intracellular responses, promoting autophagy, and enabling vacuole transport within the cell. TOLLIP is being increasingly recognized for its role in disease pathophysiology through involvement in these three primary pathways. Recent research also indicates that TOLLIP is involved in nuclear-cytoplasmic transfer, although this area requires further exploration. TOLLIP is involved in the pathophysiologic pathways associated with neurodegenerative diseases, pulmonary diseases, cardiovascular disease, inflammatory bowel disease, and malignancy. We postulate that TOLLIP plays an integral role in the disease pathophysiology of other conditions involved in vacuole trafficking and autophagy. We suggest that future research in this field should investigate the role of TOLLIP in the pathogenesis of these multiple conditions. This research has the potential to inform disease mechanisms and identify novel opportunities for therapeutic advances in multiple disease processes.

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Acknowledgments

Biorender.com was used for the creation of figures in this manuscript.

Funding

This project was supported in part by the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease. GCG is supported by the University of British Columbia Clinician Investigator Program.

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Authors and Affiliations

  1. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Xiaoyun Li, Gillian C. Goobie & Yingze Zhang

  2. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Gillian C. Goobie & Yingze Zhang

  3. Clinician Investigator Program, Department of Medicine, University of British Columbia, BC, V5Z-3X7, Vancouver, Canada

    Gillian C. Goobie

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  1. Xiaoyun Li
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XL, GG, and YZ conceptualized the overall organization. XL performed the literature search and collected the related papers. XL and GG drafted and wrote the manuscript. GG generated the figures. XL, GG, and YZ revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yingze Zhang.

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Li, X., Goobie, G.C. & Zhang, Y. Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease. J Mol Med 99, 21–31 (2021). https://doi.org/10.1007/s00109-020-01999-4

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