TLR7 /8 Activation in Immune Cells and Muscle by RNA ‐Containing Immune Complexes: Role in Inflammation and the Pathogenesis of Myositis
Article Swipe
Yin Wu
,
Aditee Deshpande
,
Nicholas Geraci
,
Petra Budde
,
Vera Sellers
,
Phanindra Velisetty
,
Chia‐Chi Sun
,
Fatima Strand
,
Carmina Bhavsar
,
Timothy B. Niewold
,
Mark A. Jensen
,
Irina Kalatskaya
,
Kavita Y. Sarin
,
David Fiorentino
,
Andrew T. Bender
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/art.42989
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/art.42989
Objective Activation of endosomal toll‐like receptors (TLRs) is one possible driver of inflammation in idiopathic inflammatory myopathies (IIM). We investigated the potential contribution of TLR7 and TLR8 to IIM pathogenesis. Methods Activation of TLR7/8 in healthy donor peripheral blood mononuclear cells (PBMCs) by immune complexes from patients with IIMs and lupus was tested. Autoantibody profiling of patient IgG samples was performed using a 1581 antigen array. TLR7 and/or TLR8 activation by RNA molecules associated with autoantibodies was assessed. Gene expression in human myoblasts and satellite cells following treatment with supernatants from TLR7/8‐activated PBMCs was evaluated by NanoString. C57BL/6 mice were dosed intramuscularly with the TLR7/8 agonist R848 and single‐cell RNA‐sequencing was performed on the muscle to ascertain the cell types responding to TLR7/8 activation and the downstream effects. Results Overall, 69 patients with IIMs were included with representation of dermatomyositis, polymyositis, and inclusion body myositis subsets. Immune complexes from patients with IIMs, as well as autoantibody‐associated RNAs histidyl‐transfer RNA, Y1, Y4, and U1, activated PBMCs to produce interferon‐α and IL‐6 via TLR7/8. Several canonical (Ro60, Ro52, and HIST1H4A) and novel (IL‐36RN) autoreactivities correlated highly with TLR7/8 activation. Supernatants from TLR7/8‐activated PBMCs had a negative impact on human myoblasts and satellite cells. Endothelial cells were activated by R848 in mouse muscle in vivo in addition to immune cells such as monocytes and macrophages. Conclusion Our results suggest that patients with IIMs have autoantibodies in their blood causing TLR7/8 activation, which leads to inflammation in muscles with potential deleterious effects. image
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/art.42989
- OA Status
- green
- Cited By
- 7
- References
- 43
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4402555087
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4402555087Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/art.42989Digital Object Identifier
- Title
-
TLR7 /8 Activation in Immune Cells and Muscle byRNA ‐Containing Immune Complexes: Role in Inflammation and the Pathogenesis of MyositisWork title - Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-09-16Full publication date if available
- Authors
-
Yin Wu, Aditee Deshpande, Nicholas Geraci, Petra Budde, Vera Sellers, Phanindra Velisetty, Chia‐Chi Sun, Fatima Strand, Carmina Bhavsar, Timothy B. Niewold, Mark A. Jensen, Irina Kalatskaya, Kavita Y. Sarin, David Fiorentino, Andrew T. BenderList of authors in order
- Landing page
-
https://doi.org/10.1002/art.42989Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/11782111Direct OA link when available
- Concepts
-
TLR7, Immune system, Inflammation, Immunology, Myositis, Peripheral blood mononuclear cell, Autoantibody, Dermatomyositis, Polymyositis, Toll-like receptor, Biology, Molecular biology, Medicine, Antibody, Innate immune system, Internal medicine, Biochemistry, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
7Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 1Per-year citation counts (last 5 years)
- References (count)
-
43Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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