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Galectin-3 Decrease...
Galectin-3 Decreases 4-1BBL Bioactivity by Crosslinking Soluble and Membrane Expressed 4-1BB
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- Nielsen, Morten Aagaard (author)
- Aarhus University,Aarhus University Hospital
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- Juul-Madsen, Kristian (author)
- Aarhus University
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- Stegmayr, John (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,Lunds Tekniska Högskola,Lung Bioengineering and Regeneration,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH
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- Gao, Chao (author)
- Harvard Medical School
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- Mehta, Akul Y. (author)
- Harvard Medical School
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- Greisen, Stinne Ravn (author)
- Aarhus University,Aarhus University Hospital
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- Kragstrup, Tue Wenzel (author)
- Aarhus University,Aarhus University Hospital
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- Hvid, Malene (author)
- Aarhus University
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- Vorup-Jensen, Thomas (author)
- Aarhus University
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- Cummings, Richard D. (author)
- Harvard Medical School
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- Leffler, Hakon (author)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
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- Deleuran, Bent Winding (author)
- Aarhus University Hospital,Aarhus University
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(creator_code:org_t)
- 2022-06-24
- 2022
- English.
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- 4-1BB
- checkpoint receptor
- Galectin-3
- inflammation
- rheumatoid arthritis
Publication and Content Type
- art (subject category)
- ref (subject category)
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Nielsen, Morten ...
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Juul-Madsen, Kri ...
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Stegmayr, John
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Gao, Chao
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Mehta, Akul Y.
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Greisen, Stinne ...
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Kragstrup, Tue W ...
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Hvid, Malene
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Vorup-Jensen, Th ...
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Cummings, Richar ...
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Leffler, Hakon
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Deleuran, Bent W ...
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and Cell Biology
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MEDICAL AND HEAL ...
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and Basic Medicine
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Frontiers in Imm ...
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Lund University