Butyrophilin 2A2 promotes T cell immunoregulation by enhancing CD45 phosphatase activity within the immune synapse Article Swipe
Shafat Ali
,
Anders H. Berg
,
M Yamashita
,
Ambart E. Covarrubias
,
Ruan Zhang
,
Vincent Dupont
,
Bongha Shin
,
Shen K. Yang
,
Ramachandran Murali
,
Madhusudhanarao Katiki
,
Margareta D. Pisarska
,
Ravi Thadhani
,
Peter S. Heeger
,
Stanley C. Jordan
,
S. Ananth Karumanchi
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.11.12.623303
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.11.12.623303
B7 costimulatory family member Butyrophilin 2A2 ( BTN2A2) is predominantly expressed by antigen presenting cells and regulates T cell immunity, but molecular mechanisms are unclear. Using immunoblots analyzing TCR-initiated signaling intermediaries, co-immunoprecipitation studies, confocal microscopy, structural modeling-guided mutational analyses, and microscale thermophoresis, we demonstrate that BTN2A2 directly interacts with CD45RO, resulting in CD45 retention within the immune synapse during TCR activation. Recombinant BTN2A2 increased murine CD4+Foxp3+ regulatory T cells (Treg) and reduced T helper 17 (Th17) cells in vitro through mechanisms dependent on CD45 phosphatase activity. BTN2A2 treatment reduced clinical expression of two murine autoimmune disease models and increased Treg/Th17 ratios. Analyses of BTN2A2-deficient animals showed exacerbated disease associated with reduced Treg/Th17 ratios. Addition of BTN2A2 to human mixed lymphocyte responses similarly enhanced human Treg and suppressed Th17 cells and was CD45 phosphatase dependent. Together, our studies identify BTN2A2 as a physiological CD45RO ligand that enhances CD45 phosphatase activity in murine and human T cells, providing mechanisms for BTN2A2-mediated amelioration of autoimmunity. Summary Butyrophilin 2A2 ameliorates autoimmunity by binding to CD45RO on activated T cell surfaces leading to dampened TCR signaling which in turn leads to expansion of T regulatory cells and reduction of Th17 differentiation.
Related Topics
Concepts
Immunological synapse
Immune system
Synapse
Cell biology
Phosphatase
T cell
Immunology
Biology
Neuroscience
Phosphorylation
T-cell receptor
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.11.12.623303
- https://www.biorxiv.org/content/biorxiv/early/2024/11/15/2024.11.12.623303.full.pdf
- OA Status
- green
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4404422724
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4404422724Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.11.12.623303Digital Object Identifier
- Title
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Butyrophilin 2A2 promotes T cell immunoregulation by enhancing CD45 phosphatase activity within the immune synapseWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
-
2024-11-15Full publication date if available
- Authors
-
Shafat Ali, Anders H. Berg, M Yamashita, Ambart E. Covarrubias, Ruan Zhang, Vincent Dupont, Bongha Shin, Shen K. Yang, Ramachandran Murali, Madhusudhanarao Katiki, Margareta D. Pisarska, Ravi Thadhani, Peter S. Heeger, Stanley C. Jordan, S. Ananth KarumanchiList of authors in order
- Landing page
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https://doi.org/10.1101/2024.11.12.623303Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/11/15/2024.11.12.623303.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2024/11/15/2024.11.12.623303.full.pdfDirect OA link when available
- Concepts
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Immunological synapse, Immune system, Synapse, Cell biology, Phosphatase, T cell, Immunology, Biology, Neuroscience, Phosphorylation, T-cell receptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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51Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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