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Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus.
Front Immunol. 2021; 12:704526.FI

Abstract

Objective

Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) is recently regarded as a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and JAK/signal transducer and activator of transcription (STAT) pathway-mediated cytokines such as type I interferons. The objective of this study was to determine whether baricitinib could effectively ameliorate SLE using a murine model.

Methods

To investigate effects of baricitinib on various autoimmune features, especially renal involvements in SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used as a lupus-prone animal model and treated with baricitinib for eight weeks. Immortalized podocytes and primary podocytes and B cells isolated from C57BL/6 mice were used to determine the in vitro efficacy of baricitinib.

Results

Baricitinib remarkably suppressed lupus-like phenotypes of MRL/lpr mice, such as splenomegaly, lymphadenopathy, proteinuria, and systemic autoimmunity including circulating autoantibodies and pro-inflammatory cytokines. It also modulated immune cell populations and effectively ameliorated renal inflammation, leading to the recovery of the expression of structural proteins in podocytes. According to in vitro experiments, baricitinib treatment could mitigate B cell differentiation and restore disrupted cytoskeletal structures of podocytes under inflammatory stimulation by blocking the JAK/STAT pathway.

Conclusions

The present study demonstrated that baricitinib could effectively attenuate autoimmune features including renal inflammation of lupus-prone mice by suppressing aberrant B cell activation and podocyte abnormalities. Thus, baricitinib as a selective JAK inhibitor could be a promising therapeutic candidate in the treatment of SLE.

Authors+Show Affiliations

The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Pub Type(s)

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

Language

eng

PubMed ID

34497607

Citation

Lee, Jaeseon, et al. "Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus." Frontiers in Immunology, vol. 12, 2021, p. 704526.
Lee J, Park Y, Jang SG, et al. Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus. Front Immunol. 2021;12:704526.
Lee, J., Park, Y., Jang, S. G., Hong, S. M., Song, Y. S., Kim, M. J., Baek, S., Park, S. H., & Kwok, S. K. (2021). Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus. Frontiers in Immunology, 12, 704526. https://doi.org/10.3389/fimmu.2021.704526
Lee J, et al. Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus. Front Immunol. 2021;12:704526. PubMed PMID: 34497607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus. AU - Lee,Jaeseon, AU - Park,Youngjae, AU - Jang,Se Gwang, AU - Hong,Seung-Min, AU - Song,Young-Seok, AU - Kim,Min-Jun, AU - Baek,SeungYe, AU - Park,Sung-Hwan, AU - Kwok,Seung-Ki, Y1 - 2021/08/23/ PY - 2021/05/03/received PY - 2021/08/04/accepted PY - 2021/9/9/entrez PY - 2021/9/10/pubmed PY - 2021/12/22/medline KW - B cell KW - baricitinib KW - podocyte KW - renal inflammation KW - systemic lupus erythematosus SP - 704526 EP - 704526 JF - Frontiers in immunology JO - Front Immunol VL - 12 N2 - Objective: Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) is recently regarded as a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and JAK/signal transducer and activator of transcription (STAT) pathway-mediated cytokines such as type I interferons. The objective of this study was to determine whether baricitinib could effectively ameliorate SLE using a murine model. Methods: To investigate effects of baricitinib on various autoimmune features, especially renal involvements in SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used as a lupus-prone animal model and treated with baricitinib for eight weeks. Immortalized podocytes and primary podocytes and B cells isolated from C57BL/6 mice were used to determine the in vitro efficacy of baricitinib. Results: Baricitinib remarkably suppressed lupus-like phenotypes of MRL/lpr mice, such as splenomegaly, lymphadenopathy, proteinuria, and systemic autoimmunity including circulating autoantibodies and pro-inflammatory cytokines. It also modulated immune cell populations and effectively ameliorated renal inflammation, leading to the recovery of the expression of structural proteins in podocytes. According to in vitro experiments, baricitinib treatment could mitigate B cell differentiation and restore disrupted cytoskeletal structures of podocytes under inflammatory stimulation by blocking the JAK/STAT pathway. Conclusions: The present study demonstrated that baricitinib could effectively attenuate autoimmune features including renal inflammation of lupus-prone mice by suppressing aberrant B cell activation and podocyte abnormalities. Thus, baricitinib as a selective JAK inhibitor could be a promising therapeutic candidate in the treatment of SLE. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/34497607/Baricitinib_Attenuates_Autoimmune_Phenotype_and_Podocyte_Injury_in_a_Murine_Model_of_Systemic_Lupus_Erythematosus_ L2 - https://doi.org/10.3389/fimmu.2021.704526 DB - PRIME DP - Unbound Medicine ER -