Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation

Sanae Ben Mkaddem (), Amaya Murua, Héloise Flament, Dimitri Titeca-Beauport, Carine Bounaix, Luca Danelli, Pierre Launay, Marc Benhamou, Ulrich Blank, Eric Daugas, Nicolas Charles and Renato C. Monteiro ()
Additional contact information
Sanae Ben Mkaddem: INSERM U1149, Centre de Recherche sur l’Inflammation
Amaya Murua: INSERM U1149, Centre de Recherche sur l’Inflammation
Héloise Flament: INSERM U1149, Centre de Recherche sur l’Inflammation
Dimitri Titeca-Beauport: INSERM U1149, Centre de Recherche sur l’Inflammation
Carine Bounaix: INSERM U1149, Centre de Recherche sur l’Inflammation
Luca Danelli: INSERM U1149, Centre de Recherche sur l’Inflammation
Pierre Launay: INSERM U1149, Centre de Recherche sur l’Inflammation
Marc Benhamou: INSERM U1149, Centre de Recherche sur l’Inflammation
Ulrich Blank: INSERM U1149, Centre de Recherche sur l’Inflammation
Eric Daugas: INSERM U1149, Centre de Recherche sur l’Inflammation
Nicolas Charles: INSERM U1149, Centre de Recherche sur l’Inflammation
Renato C. Monteiro: INSERM U1149, Centre de Recherche sur l’Inflammation

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling. These SHP-1 signatures are relevant in vivo, as Lyn deficiency exacerbates nephritis and arthritis in mice, whereas Fyn deficiency is protective. Similarly, Fyn-activating signature is detected in patients with lupus nephritis, underlining the importance of this Lyn–Fyn balance. These data show how receptors discriminate negative from positive signals that respectively result in homeostatic or inflammatory conditions.

Date: 2017
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DOI: 10.1038/s41467-017-00294-0

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