Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τετάρτη 17 Οκτωβρίου 2018

RhoH deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

Publication date: Available online 17 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Norimasa Tamehiro, Kyoko Nishida, Yu Sugita, Kunihiro Hayakawa, Hiroyo Oda, Takeshi Nitta, Miwa Nakano, Akiko Nishioka, Reiko Yanobu-Takanashi, Motohito Goto, Tadashi Okamura, Reiko Adachi, Kazunari Kondo, Akimichi Morita, Harumi Suzuki

Abstract
Background

RhoH is a membrane-bound adaptor protein involved in proximal TCR signaling. Therefore, RhoH plays critical roles in the differentiation of T cells, however the function of RhoH in effecter phase of T cell response have not been fully characterized.

Objective

To explore the role of RhoH in inflammatory immune responses, we investigated the involvement of RhoH in the pathogenesis of psoriasis.

Method

We analyzed effector T cell and systemic inflammation in wild-type and RhoH-null mice. RhoH expression in T cells in human PBMC was quantified by RT-PCR.

Results

RhoH deficiency in mice induced TH17 polarization during effector T cell differentiation, thereby inducing psoriasis-like chronic dermatitis. Ubr5 and nr2f6 expression levels decreased in RhoH-deficient T cells, resulting in increased protein levels and DNA binding activity of RORγt. The consequential increase in IL-17 and IL-22 production induced T cells to differentiate into TH17 cells. Furthermore, IL-22BP/Fc chimeric protein reduced psoriatic inflammation in RhoH deficient mice. Expression of RhoH in T cells was lower in psoriatic patients with much severe symptoms.

Conclusion

Our results indicated that RhoH inhibits TH17 differentiation and thereby plays a role in the pathogenesis of psoriasis. Additionally, IL-22BP has therapeutic potential for the treatment of psoriasis.

Graphical abstract

Graphical abstract for this article



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