Janus Kinase Inhibitor Baricitinib Modulates Human Innate and Adaptive Immune System

Frontiers in Immunology
Satoshi KuboYoshiya Tanaka

Abstract

The purpose of this study was to elucidate the mechanism of action of baricitinib on Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling, which involves in human innate and adaptive immune system. The effects of baricitinib were evaluated using human monocyte-derived dendritic cells (MoDCs), plasmacytoid dendritic cells (pDCs), B cells, and T cells. Baricitinib concentration-dependently suppressed the expression of CD80/CD86 on MoDCs and the production of type-I interferon (IFN) by pDCs. Baricitinib also suppressed the differentiation of human B cells into plasmablasts by B cell receptor and type-I IFN stimuli and inhibited the production of interleukin (IL)-6 from B cells. Human CD4+ T cells proliferated after T cell receptor stimulation with anti-CD3 and anti-CD28 antibody; however, such proliferation was suppressed by baricitinib in a concentration-dependent manner. In addition, baricitinib inhibited Th1 differentiation after IL-12 stimulation and Th17 differentiation by TGF-β1, IL-6, IL-1β, and IL-23 stimulation. Tofacitinib showed similar effects in these experiments. In naive CD4+ T cells, IFN-α and IFN-γ induced phosphorylation of STAT1, which was inhibited by baricitinib and tofacitinib....Continue Reading

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Citations

Apr 17, 2019·Expert Review of Clinical Immunology·Satoshi KuboYoshiya Tanaka
Jul 18, 2020·The Journal of Dermatology·Norito Katoh
Dec 12, 2018·American Journal of Clinical Dermatology·Helen He, Emma Guttman-Yassky
Mar 20, 2019·International Journal of Molecular Sciences·Shyi-Jou ChenHuey-Kang Sytwu
Apr 9, 2020·Frontiers in Immunology·Yongbo ZhaoLiping Jin
Mar 31, 2020·Clinical Reviews in Allergy & Immunology·Hanxiao YouXiaofeng Zeng
Jun 17, 2020·BMC Immunology·Yuya FujitaKiyoshi Migita
Jun 12, 2020·Clinical Microbiology Reviews·Joshua S DavisMichael Boyle
Dec 29, 2020·Open Medicine·Md Jahidul HasanShihan Mahmud Redwanul Huq
Dec 19, 2020·The Journal of Allergy and Clinical Immunology·Anna Sophie KlaeschenThomas Bieber
Feb 23, 2021·Frontiers in Medicine·Rita A Moura, João Eurico Fonseca
Mar 7, 2021·European Journal of Immunology·Farzan SolimaniKamran Ghoreschi
Mar 26, 2021·Journal of Endocrinological Investigation·G LiscoV Triggiani
Apr 20, 2021·Journal of Clinical Pharmacology·Sara AssadiaslMohammad Hossein Nicknam
Aug 7, 2021·Pharmaceuticals·Maha Saber-AyadQutayba Hamid
Aug 12, 2021·The Journal of Dermatological Treatment·Amelia MeloTiago Torres
Jul 21, 2020·ACS Infectious Diseases·Sirle Saul, Shirit Einav
Sep 9, 2021·The Journal of Dermatological Treatment·Milaan A ShahSteven R Feldman
Jun 16, 2021·Current Drug Research Reviews·Ekhlass UddinMd Kudrat-E-Zahan
Aug 28, 2021·JCI Insight·Annemieke SmetBenedicte Y De Winter
Nov 2, 2021·Frontiers in Immunology·Wirawan AdikusumaWei-Chiao Chang

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Methods Mentioned

BETA
FACS
FCS
flow cytometry
ELISA

Software Mentioned

Flow Jo

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