The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis.
Animals
Cell Differentiation
/ immunology
Cell Lineage
Dexamethasone
/ pharmacology
Humans
Interleukin-4
/ metabolism
Killer Cells, Natural
/ immunology
Lectins, C-Type
/ metabolism
Lymphocyte Activation
/ immunology
Macrophage Activation
/ immunology
Macrophages
/ cytology
Membrane Proteins
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Neoplasm Metastasis
/ immunology
Neoplasms
/ immunology
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
13
11
2017
accepted:
02
05
2019
pubmed:
3
7
2019
medline:
20
11
2019
entrez:
3
7
2019
Statut:
ppublish
Résumé
The plasma membrane tetraspan molecule MS4A4A is selectively expressed by macrophage-lineage cells, but its function is unknown. Here we report that MS4A4A was restricted to murine and human mononuclear phagocytes and was induced during monocyte-to-macrophage differentiation in the presence of interleukin 4 or dexamethasone. Human MS4A4A was co-expressed with M2/M2-like molecules in subsets of normal tissue-resident macrophages, infiltrating macrophages from inflamed synovium and tumor-associated macrophages. MS4A4A interacted and colocalized with the β-glucan receptor dectin-1 in lipid rafts. In response to dectin-1 ligands, Ms4a4a-deficient macrophages showed defective signaling and defective production of effector molecules. In experimental models of tumor progression and metastasis, Ms4a4a deficiency in macrophages had no impact on primary tumor growth, but was essential for dectin-1-mediated activation of macrophages and natural killer (NK) cell-mediated metastasis control. Thus, MS4A4A is a tetraspan molecule selectively expressed in macrophages during differentiation and polarization, essential for dectin-1-dependent activation of NK cell-mediated resistance to metastasis.
Identifiants
pubmed: 31263276
doi: 10.1038/s41590-019-0417-y
pii: 10.1038/s41590-019-0417-y
pmc: PMC7176488
mid: EMS86222
doi:
Substances chimiques
CLEC7A protein, human
0
IL4 protein, human
0
Lectins, C-Type
0
MS4A4A protein, human
0
Membrane Proteins
0
Interleukin-4
207137-56-2
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1012-1022Subventions
Organisme : Versus Arthritis
ID : 20022
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 21890
Pays : United Kingdom
Organisme : European Research Council
ID : 669415
Pays : International
Organisme : Medical Research Council
ID : G0800648
Pays : United Kingdom
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