Galectin-3 Decreases 4-1BBL Bioactivity by Crosslinking Soluble and Membrane Expressed 4-1BB
(2022) In Frontiers in Immunology 13.- Abstract
4-1BB is a T cell costimulatory receptor and a member of the tumor necrosis factor receptor superfamily. Here, we show that Galectin-3 (Gal-3) decreases the cellular response to its ligand (4-1BBL). Gal-3 binds to both soluble 4-1BB (s4-1BB) and membrane-bound 4-1BB (mem4-1BB), without blocking co-binding of 4-1BBL. In plasma, we detected complexes composed of 4-1BB and Gal-3 larger than 100 nm in size; these complexes were reduced in synovial fluid from rheumatoid arthritis. Both activated 4-1BB+ T cells and 4-1BB-transfected HEK293 cells depleted these complexes from plasma, followed by increased expression of 4-1BB and Gal-3 on the cell surface. The increase was accompanied by a 4-fold decrease in TNFα production by the... (More)
4-1BB is a T cell costimulatory receptor and a member of the tumor necrosis factor receptor superfamily. Here, we show that Galectin-3 (Gal-3) decreases the cellular response to its ligand (4-1BBL). Gal-3 binds to both soluble 4-1BB (s4-1BB) and membrane-bound 4-1BB (mem4-1BB), without blocking co-binding of 4-1BBL. In plasma, we detected complexes composed of 4-1BB and Gal-3 larger than 100 nm in size; these complexes were reduced in synovial fluid from rheumatoid arthritis. Both activated 4-1BB+ T cells and 4-1BB-transfected HEK293 cells depleted these complexes from plasma, followed by increased expression of 4-1BB and Gal-3 on the cell surface. The increase was accompanied by a 4-fold decrease in TNFα production by the 4-1BBhighGal-3+ T cells, after exposure to 4-1BB/Gal-3 complexes. In RA patients, complexes containing 4-1BB/Gal-3 were dramatically reduced in both plasma and SF compared with healthy plasma. These results support that Gal-3 binds to 4-1BB without blocking the co-binding of 4-1BBL. Instead, Gal-3 leads to formation of large soluble 4-1BB/Gal-3 complexes that attach to mem4-1BB on the cell surfaces, resulting in suppression of 4-1BBL’s bioactivity.
(Less)
- author
- organization
- publishing date
- 2022-06-24
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 4-1BB, checkpoint receptor, Galectin-3, inflammation, rheumatoid arthritis
- in
- Frontiers in Immunology
- volume
- 13
- article number
- 915890
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85134067706
- pmid:35812455
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2022.915890
- language
- English
- LU publication?
- yes
- id
- e17c4fa6-4098-4455-818e-3ad056a46f95
- date added to LUP
- 2022-10-06 09:23:13
- date last changed
- 2024-09-20 05:05:07
@article{e17c4fa6-4098-4455-818e-3ad056a46f95, abstract = {{<p>4-1BB is a T cell costimulatory receptor and a member of the tumor necrosis factor receptor superfamily. Here, we show that Galectin-3 (Gal-3) decreases the cellular response to its ligand (4-1BBL). Gal-3 binds to both soluble 4-1BB (s4-1BB) and membrane-bound 4-1BB (mem4-1BB), without blocking co-binding of 4-1BBL. In plasma, we detected complexes composed of 4-1BB and Gal-3 larger than 100 nm in size; these complexes were reduced in synovial fluid from rheumatoid arthritis. Both activated 4-1BB<sup>+</sup> T cells and 4-1BB-transfected HEK293 cells depleted these complexes from plasma, followed by increased expression of 4-1BB and Gal-3 on the cell surface. The increase was accompanied by a 4-fold decrease in TNFα production by the 4-1BB<sup>high</sup>Gal-3<sup>+</sup> T cells, after exposure to 4-1BB/Gal-3 complexes. In RA patients, complexes containing 4-1BB/Gal-3 were dramatically reduced in both plasma and SF compared with healthy plasma. These results support that Gal-3 binds to 4-1BB without blocking the co-binding of 4-1BBL. Instead, Gal-3 leads to formation of large soluble 4-1BB/Gal-3 complexes that attach to mem4-1BB on the cell surfaces, resulting in suppression of 4-1BBL’s bioactivity.</p>}}, author = {{Nielsen, Morten Aagaard and Juul-Madsen, Kristian and Stegmayr, John and Gao, Chao and Mehta, Akul Y. and Greisen, Stinne Ravn and Kragstrup, Tue Wenzel and Hvid, Malene and Vorup-Jensen, Thomas and Cummings, Richard D. and Leffler, Hakon and Deleuran, Bent Winding}}, issn = {{1664-3224}}, keywords = {{4-1BB; checkpoint receptor; Galectin-3; inflammation; rheumatoid arthritis}}, language = {{eng}}, month = {{06}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{Galectin-3 Decreases 4-1BBL Bioactivity by Crosslinking Soluble and Membrane Expressed 4-1BB}}, url = {{http://dx.doi.org/10.3389/fimmu.2022.915890}}, doi = {{10.3389/fimmu.2022.915890}}, volume = {{13}}, year = {{2022}}, }