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1.
Nat Immunol ; 25(7): 1193-1206, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38834865

RESUMEN

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 IKKß-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.


Asunto(s)
Movimiento Celular , Células Dendríticas , Homeostasis , Ganglios Linfáticos , Ratones Endogámicos C57BL , Receptores CCR7 , Animales , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/citología , Receptores CCR7/metabolismo , Ratones , Movimiento Celular/inmunología , Forma de la Célula , FN-kappa B/metabolismo , Ratones Noqueados , Transducción de Señal/inmunología , Quinasa I-kappa B/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo
2.
Sci Adv ; 7(34)2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34407944

RESUMEN

The COVID-19 pandemic has spread worldwide, yet the role of antiviral T cell immunity during infection and the contribution of immune checkpoints remain unclear. By prospectively following a cohort of 292 patients with melanoma, half of which treated with immune checkpoint inhibitors (ICIs), we identified 15 patients with acute or convalescent COVID-19 and investigated their transcriptomic, proteomic, and cellular profiles. We found that ICI treatment was not associated with severe COVID-19 and did not alter the induction of inflammatory and type I interferon responses. In-depth phenotyping demonstrated expansion of CD8 effector memory T cells, enhanced T cell activation, and impaired plasmablast induction in ICI-treated COVID-19 patients. The evaluation of specific adaptive immunity in convalescent patients showed higher spike (S), nucleoprotein (N), and membrane (M) antigen-specific T cell responses and similar induction of spike-specific antibody responses. Our findings provide evidence that ICI during COVID-19 enhanced T cell immunity without exacerbating inflammation.


Asunto(s)
COVID-19/inmunología , Inhibidores de Puntos de Control Inmunológico/inmunología , Melanoma/inmunología , SARS-CoV-2/inmunología , Linfocitos T/inmunología , Inmunidad Adaptativa/efectos de los fármacos , Inmunidad Adaptativa/inmunología , Anciano , Anticuerpos Antivirales/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , COVID-19/complicaciones , COVID-19/virología , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Memoria Inmunológica/efectos de los fármacos , Memoria Inmunológica/inmunología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Masculino , Melanoma/complicaciones , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/virología
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