Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells
(2019) In Communications Biology 2.- Abstract
Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and Drosophila protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data... (More)
Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and Drosophila protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in human myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance.
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- author
- Mehmeti, Meliha LU ; Bergenfelz, Caroline LU ; Källberg, Eva LU ; Millrud, Camilla Rydberg LU ; Björk, Per ; Ivars, Fredrik LU ; Johansson-Lindbom, Bengt LU ; Kjellström, Sven LU ; André, Ingemar LU and Leandersson, Karin LU
- organization
-
- Cancer Immunology, Malmö (research group)
- Experimental Infection Medicine, Malmö (research group)
- Immunology (research group)
- Adaptive Immunity (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Centre for Analysis and Synthesis
- eSSENCE: The e-Science Collaboration
- Biochemistry and Structural Biology
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Communications Biology
- volume
- 2
- article number
- 176
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:31098409
- scopus:85071184154
- ISSN
- 2399-3642
- DOI
- 10.1038/s42003-019-0432-4
- language
- English
- LU publication?
- yes
- id
- 2a6a610a-cd0e-481f-80b7-030eb15a6b7e
- alternative location
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509336/
- date added to LUP
- 2019-05-22 14:13:22
- date last changed
- 2024-10-24 02:44:44
@article{2a6a610a-cd0e-481f-80b7-030eb15a6b7e, abstract = {{<p>Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and Drosophila protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in human myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance.</p>}}, author = {{Mehmeti, Meliha and Bergenfelz, Caroline and Källberg, Eva and Millrud, Camilla Rydberg and Björk, Per and Ivars, Fredrik and Johansson-Lindbom, Bengt and Kjellström, Sven and André, Ingemar and Leandersson, Karin}}, issn = {{2399-3642}}, language = {{eng}}, publisher = {{Nature Publishing Group}}, series = {{Communications Biology}}, title = {{Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells}}, url = {{http://dx.doi.org/10.1038/s42003-019-0432-4}}, doi = {{10.1038/s42003-019-0432-4}}, volume = {{2}}, year = {{2019}}, }