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

Carolina Brescia; Vincenzo Dattilo; Lucia D'Antona; Emanuela Chiarella; Rossana Tallerico; Salvatore Audia; Valentina Rocca; Rodolfo Iuliano; Francesco Trapasso; Nicola Perrotti; Rosario Amato

doi:10.3389/fimmu.2023.1213805

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

Front Immunol. 2023 Jun 27:14:1213805. doi: 10.3389/fimmu.2023.1213805. eCollection 2023.

Authors

Carolina Brescia^{1

2}, Vincenzo Dattilo³, Lucia D'Antona^{1

4}, Emanuela Chiarella³, Rossana Tallerico⁵, Salvatore Audia^{1

2}, Valentina Rocca^{1

4}, Rodolfo Iuliano^{1

4}, Francesco Trapasso^{3

4}, Nicola Perrotti^{1

4}, Rosario Amato^{1

2

4}

Affiliations

¹ Department of Health Science, Medical School, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
² Immuno-Genetics Lab, Department of Health Science, Medical School, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
³ Department of Experimental and Clinical Medicine, Medical School, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
⁴ Medical Genetics Unit, University Hospital, Medical School, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
⁵ Microbiology and Virology Unit, "Pugliese-Ciaccio" Hospital, Catanzaro, Italy.

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 RORγt activation. In this light, RANBP1 represents the missing piece, in an essential and rate-limiting manner, underlying the Th17⁺ immune asset.

Keywords: FOXO1; RANBP1; SGK1; Th17+; nuclear transport.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Nucleus / metabolism
Cytoplasm / metabolism
Nuclear Proteins* / genetics
ran GTP-Binding Protein* / metabolism

Substances

ran-binding protein 1
ran GTP-Binding Protein
Nuclear Proteins

Grants and funding

This work was supported by the AIRC (Italian Association for Cancer Research) grants 20946, 16971-21495, by Fujirebio’s liberal contribution, and a generous donation from the Stillitani family, in memory of Carmelo. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.