RESUMEN
The thymus is a primary lymphoid organ that is essential for the establishment of adaptive immunity through generation of immunocompetent T cells. In response to various stress signals, the thymus undergoes acute but reversible involution. However, the mechanisms governing its recovery are incompletely understood. Here, we used a dexamethasone-induced acute thymic involution mouse model to investigate how thymic hematopoietic cells (excluding T cells) contribute to thymic regeneration. scRNA-seq analysis revealed marked transcriptional and cellular changes in various thymic populations and highlighted thymus-resident innate lymphoid cells type 2 (ILC2) as a key cell type involved in the response to damage. We identified that ILC2 are activated by the alarmins IL-25 and IL-33 produced in response to tissue damage by thymic tuft cells and fibroblasts, respectively. Moreover, using mouse models deficient in either tuft cells and/or IL-33, we found that these alarmins are required for effective thymus regeneration after dexamethasone-induced damage. We also demonstrate that upon their damage-dependent activation, thymic ILC2 produce several effector molecules linked to tissue regeneration, such as amphiregulin and IL-13, which in turn promote thymic epithelial cell differentiation. Collectively, our study elucidates a previously undescribed role for thymic tuft cells and fibroblasts in thymus regeneration through activation of the type 2 immune response.
Asunto(s)
Inmunidad Innata , Interleucina-33 , Ratones , Animales , Linfocitos , Células en Penacho , Alarminas , Modelos Animales de Enfermedad , Fibroblastos , Dexametasona/farmacologíaRESUMEN
Resonance enhancement of high-order harmonic generation has recently been found in the interaction of intense ultrashort laser pulses with laser ablated plasma plumes. It is a promising route towards the production of an intense and coherent extreme ultraviolet radiation source. However, the mechanism of this resonance enhancement is still not clear. There are two possible explanations; one relies on a better recombination cross section through an autoionization state in the single-atom response. The other relies on improved phase matching conditions around the resonance. Here, we try to discriminate between these two conjectures by measuring coherence lengths of the harmonics, both on resonance and off resonance. Our findings support the single-atom response hypothesis.