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Cited by 79Immune Response and InflammationInflammasome and immune disordersNF-κB Signaling Pathways

TIRAP in the Mechanism of Inflammation

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Rajpoot, Sajjan, Wary, Kishore K., Ibbott, Rachel, Liu, Dongfang, Saqib, Uzma, Thurston, Teresa L. M., Baig, Mirza S.·2021·Frontiers in Immunology
DOI 10.3389/fimmu.2021.697588PMC PMC8297548
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Abstract

The Toll-interleukin-1 Receptor (TIR) domain-containing adaptor protein (TIRAP) represents a key intracellular signalling molecule regulating diverse immune responses. Its capacity to function as an adaptor molecule has been widely investigated in relation to Toll-like Receptor (TLR)-mediated innate immune signalling. Since the discovery of TIRAP in 2001, initial studies were mainly focused on its role as an adaptor protein that couples Myeloid differentiation factor 88 (MyD88) with TLRs, to activate MyD88-dependent TLRs signalling. Subsequent studies delineated TIRAP’s role as a transducer of signalling events through its interaction with non-TLR signalling mediators. Indeed, the ability of TIRAP to interact with an array of intracellular signalling mediators suggests its central role in various immune responses. Therefore, continued studies that elucidate the molecular basis of various TIRAP-protein interactions and how they affect the signalling magnitude, should provide key information on the inflammatory disease mechanisms. This review summarizes the TIRAP recruitment to activated receptors and discusses the mechanism of interactions in relation to the signalling that precede acute and chronic inflammatory diseases. Furthermore, we highlighted the significance of TIRAP-TIR domain containing binding sites for several intracellular inflammatory signalling molecules. Collectively, we discuss the importance of the TIR domain in TIRAP as a key interface involved in protein interactions which could hence serve as a therapeutic target to dampen the extent of acute and chronic inflammatory conditions.

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  • RAGE was suggested to induce MyD88-dependent proinflammatory signaling, with TIRAP acting as a bridge, similar to TLR signaling.

    “In addition, RAGE was also suggested to induce MyD88-dependent proinflammatory signaling, with TIRAP acting as a bridge, which is similar to TLR signaling.326”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [326]

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Cited by

Sorted by citations

Authors
Rajpoot, S., Wary, K. K., Ibbott, R., Liu, D., Saqib, U., Thurston, T. L. M., & Baig, M. S.
Affiliations
  • Indian Institute of Technology Indore (IN)
  • University of Illinois Chicago (US)
  • Imperial College London (GB)
  • Rutgers, The State University of New Jersey (US)
Corresponding author
  • Thurston, Teresa L. M.
  • Baig, Mirza S.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2021-07-08
Volume
12
Pages
697588-697588
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2021.697588
PMC
PMC8297548
OpenAlex
W3181024808
Cited by
79
References
6
Citations by year
2026: 22 · 2025: 11 · 2024: 15 · 2023: 17 · 2022: 12 · 2021: 2
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • Indian Institute of Technology Indore
  • Directorate for Biological Sciences
  • Biotechnology and Biological Sciences Research Council (BB/R011834/1, BB/R011834/)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
TIRAP, Toll/interleukin-1 receptor domain, MyD88, Toll-like receptor signaling, innate immunity, adaptor proteins, protein-protein interaction, TIR domain, inflammatory signalling, chronic inflammation, acute inflammation, therapeutic target
MeSH terms
Receptor for Advanced Glycation End Products, Agammaglobulinaemia Tyrosine Kinase, Animals, Carrier Proteins, Humans, Immunity, Innate, Inflammation, Membrane Glycoproteins, Models, Biological, Signal Transduction, Receptors, Interleukin-1, Protein Kinase C-delta, Class Ia Phosphatidylinositol 3-Kinase, Protein Interaction Maps

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