“To the clinician, systemic lupus erythematosus is important because it is a potentially fatal disease that is easily confused with many other disorders. To the immunologist, lupus is intriguing because all the key components of the immune system are involved in the underlying mechanisms of the disease.”(Anisur Rahman, Ph.D., and David A. Isenberg, M.D. N Engl J Med. 2008 Feb 28;358(9):929-39.). I have studied this devastating but intellectually challenging disease more than 10 years. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of great diversity of autoantibodies against nucleic acids (DNA and RNA) and other autoantigens. The autoantibodies form immune complexes that deposit in various tissues including the kidney, causing inflammation and end-organ damage. Current medications are only partially effective and have severe side effects.
My recent interest is neutrophil activation induced by immune complexes. Studies have shown that neutrophils release reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) upon stimulation with RNA-containing immune complexes. My new goal is to investigate whether other immune complexes from SLE patients can activate neutrophils, and what kind of signaling pathways are involved in the activation.
I am also interested in the role of interferon regulatory factor-5 (IRF5) in the pathogenesis of SLE. Genetic studies have shown that mutations of IRF5 are associated with the disease severity of SLE. Using IRF5-deficient mice and lupus-prone mice, we have shown that IRF5 is a critical regulatory of SLE. In addition, we have shown that sera from SLE patients are able to activate plasmacytoid dendritic cells (pDC) to induce type I IFN , which is a pathogenic cytokines in SLE. We demonstrated that the type I IFN production from pDC is dependent on toll-like receptor-7 (TLR7) and IRF5. We investigate whether IRF5 is involved in the activation of B cells and T cells.
- Boston Medical Center
- Kyoto University, PhD
- Kyoto University, MS
- Kyoto University, BS
- Published on 4/11/2017
Choo MK, Sano Y, Kim C, Yasuda K, Li XD, Lin X, Stenzel-Poore M, Alexopoulou L, Ghosh S, Latz E, Rifkin IR, Chen ZJ, Stewart GC, Chong H, Park JM. TLR sensing of bacterial spore-associated RNA triggers host immune responses with detrimental effects. J Exp Med. 2017 May 01; 214(5):1297-1311. PMID: 28400473.
- Published on 12/1/2015
Duffau P, Menn-Josephy H, Cuda CM, Dominguez S, Aprahamian TR, Watkins AA, Yasuda K, Monach P, Lafyatis R, Rice LM, Kenneth Haines G, Gravallese EM, Baum R, Richez C, Perlman H, Bonegio RG, Rifkin IR. Promotion of Inflammatory Arthritis by Interferon Regulatory Factor 5 in a Mouse Model. Arthritis Rheumatol. 2015 Dec; 67(12):3146-57. PMID: 26315890.
- Published on 1/16/2015
Watkins AA, Yasuda K, Wilson GE, Aprahamian T, Xie Y, Maganto-Garcia E, Shukla P, Oberlander L, Laskow B, Menn-Josephy H, Wu Y, Duffau P, Fried SK, Lichtman AH, Bonegio RG, Rifkin IR. IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis. J Immunol. 2015 Feb 15; 194(4):1467-79. PMID: 25595782.
- Published on 10/3/2014
Ericson JA, Duffau P, Yasuda K, Ortiz-Lopez A, Rothamel K, Rifkin IR, Monach PA. Gene expression during the generation and activation of mouse neutrophils: implication of novel functional and regulatory pathways. PLoS One. 2014; 9(10):e108553. PMID: 25279834.
- Published on 7/30/2014
Yasuda K, Watkins AA, Kochar GS, Wilson GE, Laskow B, Richez C, Bonegio RG, Rifkin IR. Interferon regulatory factor-5 deficiency ameliorates disease severity in the MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2. PLoS One. 2014; 9(7):e103478. PMID: 25076492.
- Published on 1/4/2013
Yasuda K, Nündel K, Watkins AA, Dhawan T, Bonegio RG, Ubellacker JM, Marshak-Rothstein A, Rifkin IR. Phenotype and function of B cells and dendritic cells from interferon regulatory factor 5-deficient mice with and without a mutation in DOCK2. Int Immunol. 2013 May; 25(5):295-306. PMID: 23291967.
- Published on 12/9/2009
Richez C, Yasuda K, Bonegio RG, Watkins AA, Aprahamian T, Busto P, Richards RJ, Liu CL, Cheung R, Utz PJ, Marshak-Rothstein A, Rifkin IR. IFN regulatory factor 5 is required for disease development in the FcgammaRIIB-/-Yaa and FcgammaRIIB-/- mouse models of systemic lupus erythematosus. J Immunol. 2010 Jan 15; 184(2):796-806. PMID: 20007534.
- Published on 7/31/2009
Yasuda K, Richez C, Uccellini MB, Richards RJ, Bonegio RG, Akira S, Monestier M, Corley RB, Viglianti GA, Marshak-Rothstein A, Rifkin IR. Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing immune complexes. J Immunol. 2009 Sep 1; 183(5):3109-17. PMID: 19648272.
- Published on 7/8/2009
Green NM, Laws A, Kiefer K, Busconi L, Kim YM, Brinkmann MM, Trail EH, Yasuda K, Christensen SR, Shlomchik MJ, Vogel S, Connor JH, Ploegh H, Eilat D, Rifkin IR, van Seventer JM, Marshak-Rothstein A. Murine B cell response to TLR7 ligands depends on an IFN-beta feedback loop. J Immunol. 2009 Aug 1; 183(3):1569-76. PMID: 19587008.
- Published on 5/28/2009
Lenert P, Yasuda K, Busconi L, Nelson P, Fleenor C, Ratnabalasuriar RS, Nagy PL, Ashman RF, Rifkin IR, Marshak-Rothstein A. DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas(lpr/lpr) mice in vivo. Arthritis Res Ther. 2009; 11(3):R79. PMID: 19476613.
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