The Th17(+) arrangement is critical for orchestrating both innate and acquired immune responses. In this context, the serum and glucocorticoid regulated kinase 1 (SGK1) exerts a key role in the governance of IL-23R-dependent Th17(+) maturation, through the phosphorylation-dependent control of FOXO1 localization. Our previous work has shown that some of the SGK1-key functions are dependent on RAN-binding protein 1 (RANBP1), a terminal gene in the nuclear transport regulation. Here, we show that RANBP1, similarly to SGK1, is modulated during Th17(+) differentiation and that RANBP1 fluctuations mediate the SGK1-dependent effects on Th17(+) maturation. RANBP1, as the final effector of the SGK1 pathway, affects FOXO1 transport from the nucleus to the cytoplasm, thus enabling ROR & gamma;t activation. In this light, RANBP1 represents the missing piece, in an essential and rate-limiting manner, underlying the Th17(+) immune asset.

RANBP1, a member of the nuclear-cytoplasmic trafficking-regulator complex, is the terminal-striking point of the SGK1-dependent Th17+ pathological differentiation

Brescia, Carolina;Dattilo, Vincenzo;D'Antona, Lucia;Chiarella, Emanuela;Tallerico, Rossana;Rocca, Valentina;Iuliano, Rodolfo;Trapasso, Francesco;Perrotti, Nicola;Amato, Rosario
2023-01-01

Abstract

The Th17(+) arrangement is critical for orchestrating both innate and acquired immune responses. In this context, the serum and glucocorticoid regulated kinase 1 (SGK1) exerts a key role in the governance of IL-23R-dependent Th17(+) maturation, through the phosphorylation-dependent control of FOXO1 localization. Our previous work has shown that some of the SGK1-key functions are dependent on RAN-binding protein 1 (RANBP1), a terminal gene in the nuclear transport regulation. Here, we show that RANBP1, similarly to SGK1, is modulated during Th17(+) differentiation and that RANBP1 fluctuations mediate the SGK1-dependent effects on Th17(+) maturation. RANBP1, as the final effector of the SGK1 pathway, affects FOXO1 transport from the nucleus to the cytoplasm, thus enabling ROR & gamma;t activation. In this light, RANBP1 represents the missing piece, in an essential and rate-limiting manner, underlying the Th17(+) immune asset.
2023
FOXO1
RANBP1
SGK1
Th17+
nuclear transport
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/88057
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact