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Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

Tamehiro, Norimasa, Nishida, Kyoko, Sugita, Yu, Hayakawa, Kunihiro, Oda, Hiroyo, Nitta, Takeshi, Nakano, Miwa, Nishioka, Akiko, Yanobu-Takanashi, Reiko, Goto, Motohito, Okamura, Tadashi, Adachi, Reiko, Kondo, Kazunari, Morita, Akimichi, Suzuki, Harumi·2019·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2018.09.032
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Abstract

Background Ras homolog gene family H (RhoH) is a membrane-bound adaptor protein involved in proximal T-cell receptor signaling. Therefore RhoH plays critical roles in the differentiation of T cells; however, the function of RhoH in the effecter phase of the T-cell response has not been fully characterized. Objective We sought to explore the role of RhoH in inflammatory immune responses and investigated the involvement of RhoH in the pathogenesis of psoriasis. Methods We analyzed effector T-cell and systemic inflammation in wild-type and RhoH-null mice. RhoH expression in T cells in human PBMCs was quantified by using RT-PCR. Results RhoH deficiency in mice induced T H 17 polarization during effector T-cell differentiation, thereby inducing psoriasis-like chronic dermatitis. Ubiquitin protein ligase E3 component N-recognin 5 (Ubr5) and nuclear receptor subfamily 2 group F member 6 (Nr2f6) expression levels decreased in RhoH-deficient T cells, resulting in increased protein levels and DNA binding activity of retinoic acid-related orphan receptor γt. The consequential increase in IL-17 and IL-22 production induced T cells to differentiate into T H 17 cells. Furthermore, IL-22 binding protein/Fc chimeric protein reduced psoriatic inflammation in RhoH-deficient mice. Expression of RhoH in T cells was lower in patients with psoriasis with very severe symptoms. Conclusion Our results indicate that RhoH inhibits T H 17 differentiation and thereby plays a role in the pathogenesis of p…

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Cited by

Metadata

Authors
Tamehiro, N., Nishida, K., Sugita, Y., Hayakawa, K., Oda, H., Nitta, T., Nakano, M., Nishioka, A., Yanobu-Takanashi, R., Goto, M., Okamura, T., Adachi, R., Kondo, K., Morita, A., & Suzuki, H.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2019-05
Volume
143
Issue
5
Pages
1878-1891
ISSN
0091-6749
DOI
10.1016/j.jaci.2018.09.032
Cited by
25
References
7
Language
en
Licence
Funders
  • Uehara Memorial Foundation
  • Takeda Science Foundation
  • Manpei Suzuki Diabetes Foundation
  • National Center for Global Health and Medicine (25-103, 26-106)
  • Ministry of Education, Culture, Sports, Science and Technology

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