Publication: Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes.

Publié dans: Nat Immunol 2024 Jul; 25(7): 1193-1206

Auteurs: Alraies Z, Rivera CA, Delgado MG, Sanséau D, Maurin M, Amadio R, Maria Piperno G, Dunsmore G, Yatim A, Lacerda Mariano L, Kniazeva A, Calmettes V, Sáez PJ, Williart A, Popard H, Gratia M, Lamiable O, Moreau A, Fusilier Z, Crestey L, Albaud B, Legoix P, Dejean AS, Le Dorze AL, Nakano H, Cook DN, Lawrence T, Manel N, Benvenuti F, Ginhoux F, Moreau HD, P F Nader G, Piel M, Lennon-Duménil AM

Résumé

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA2, requires nuclear envelope tensioning and is finely tuned by the ARP2/3 actin nucleation complex. We also show that this shape-sensing axis reprograms dendritic cell transcription by activating an IKKβ-NF-κB-dependent pathway known to control their tolerogenic potential. These results indicate that cell shape changes experienced by immune cells can define their migratory behavior and immunoregulatory properties and reveal a contribution of the physical properties of tissues to adaptive immunity.

Lien vers Pubmed [PMID] – 38834865

Lien vers HAL – inserm-04676351

Lien vers le DOI – 10.1038/s41590-024-01856-3