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          Labs @ NIAMS
          NIAMS Scientific Advances
          Itaconic Acid Derivative Is Effective in Keeping Established Murine Lupus Under Control








NIAMS Advances


Itaconic Acid Derivative Is Effective in Keeping Established Murine Lupus Under Control July 6, 2022
                                TRANSLATIONAL
        Mariana J. Kaplan, M.D.
                                          |
              Systemic Autoimmunity Branch
                                          |
              NIAMS IRP
        Description

Itaconic acid, a mitochondrial immune metabolite, is known to suppress inflammatory and oxidative stress responses. In this study, the authors showed that a derivative of itaconic acid, 4-octyl itaconate, significantly reduced murine lupus through modulation of the JAK/STAT pathways. This opens the possibility of further exploring itaconate-derived agents for lupus therapeutics.

What is exciting about this article?

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder associated with severe morbidity and mortality. The first line of treatment to control systemic inflammation in SLE is immunosuppressive drugs and immunomodulators. Finding a novel drug that has minimal side effects is of critical importance in the treatment of this disease. This study showed that therapeutic use of an itaconic acid derivative improved disease outcomes in mice with established lupus, paving the way for a potential treatment strategy for SLE and other autoimmune diseases.

How does this fit into the larger NIAMS portfolio?

The focus of this study is to describe potential mechanisms of immune dysregulation and identify novel therapeutic targets to prevent premature vascular damage in systemic autoimmune diseases like SLE. The study findings provide evidence that itaconate-derived therapeutics may have an important role in autoimmune disorders.

Grant support

AR041199
        Research Areas:
            Autoimmunity
      Cell Biology
      Immunology
      Molecular Biology and Biochemistry
                                        Reference:
            Modulation of the Itaconate Pathway Attenuates Murine Lupus.

    Blanco LP, Patino-Martinez E, Nakabo S, Zhang M, Pedersen HL, Wang X, Carmona-Rivera C, Claybaugh D, Yu ZX, Desta E, Kaplan MJ
        

                    Arthritis Rheumatol.
        
                    2022 Dec;
        
                    74(12).
        
                    doi: 10.1002/art.42284
                            PMID: 35791960
        Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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