A20's linear ubiquitin-binding motif restrains pathogenic activation of Th17 cells and IL-22-driven enteritis. Bowman CJ, Stibor DM, Sun X, Lenci N, Shimizu H, Yamashita EF, Advincula R, Kim MC, Turnbaugh JA, Sun Y, Razani B, Turnbaugh PJ, Ye CJ, Malynn BA, Ma A. J Clin Invest. 2025 Sep 2;135(17):e187499 https://pubmed.ncbi.nlm.nih.gov/40892518/
Unrestrained MyD88 Signaling in A20-Deficient Keratinocytes Triggers T-Cell-Dependent Psoriatic Arthritis-Like Disease. Tobias R, Kumar S, Liu J, Lenci N, Gharabi A, Stibor D, Advincula R, Achacoso P, Huang ZM, Bowman C, Ricardo-Gonzalez R, Nakamura MC, Liao W, Malynn BA, Ma A, Razani B. J Invest Dermatol. 2025 Dec;145(12):2998-3010. https://pubmed.ncbi.nlm.nih.gov/40316204/
Modulating Cytokines as Treatment for Autoimmune Diseases and Cancer. Mortier E, Ma A, Malynn BA, Neurath MF. Front Immunol. 2020 Oct 15;11:608636. https://pubmed.ncbi.nlm.nih.gov/33178231/
Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation. Razani B, Whang MI, Kim FS, Nakamura MC, Sun X, Advincula R, Turnbaugh JA, Pendse M, Tanbun P, Achacoso P, Turnbaugh PJ, Malynn BA, Ma A. Nat Immunol. 2020 04; 21(4):422-433. https://pubmed.ncbi.nlm.nih.gov/32205880/
The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis. Onizawa M, Oshima S, Schulze-Topphoff U, Oses-Prieto JA, Lu T, Tavares R, Prodhomme T, Duong B, Whang MI, Advincula R, Agelidis A, Barrera J, Wu H, Burlingame A, Malynn BA, Zamvil SS, Ma A. Nat Immunol. 2015 Jun;16(6):618-27. https://pubmed.ncbi.nlm.nih.gov/25939025/
A20 restricts ubiquitination of pro-interleukin-1β protein complexes and suppresses NLRP3 inflammasome activity. Duong BH, Onizawa M, Oses-Prieto JA, Advincula R, Burlingame A, Malynn BA, Ma A. Immunity. 2015 Jan 20;42(1):55-67. https://pubmed.ncbi.nlm.nih.gov/25607459/
Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme. Lu TT, Onizawa M, Hammer GE, Turer EE, Yin Q, Damko E, Agelidis A, Shifrin N, Advincula R, Barrera J, Malynn BA, Wu H, Ma A. Immunity. 2013 May 23;38(5):896-905. https://pubmed.ncbi.nlm.nih.gov/23602765/
Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA, Reizis B, DeFranco A, Criswell LA, Nakamura MC, Ma A. Nat Immunol. 2011 Oct 23;12(12):1184-93. https://pubmed.ncbi.nlm.nih.gov/22019834/
The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity. Tavares RM, Turer EE, Liu CL, Advincula R, Scapini P, Rhee L, Barrera J, Lowell CA, Utz PJ, Malynn BA, Ma A. Immunity. 2010 Aug 27;33(2):181-91. https://pubmed.ncbi.nlm.nih.gov/20705491/
ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development. Oshima S, Turer EE, Callahan JA, Chai S, Advincula R, Barrera J, Shifrin N, Lee B, Benedict Yen TS, Woo T, Malynn BA, Ma A. Nature. 2009 Feb 12;457(7231):906-9. https://pubmed.ncbi.nlm.nih.gov/19060883/
The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals. Hitotsumatsu O, Ahmad RC, Tavares R, Wang M, Philpott D, Turer EE, Lee BL, Shiffin N, Advincula R, Malynn BA, Werts C, Ma A. Immunity. 2008 Mar;28(3):381-90. https://pubmed.ncbi.nlm.nih.gov/18342009/
The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Boone DL, Turer EE, Lee EG, Ahmad RC, Wheeler MT, Tsui C, Hurley P, Chien M, Chai S, Hitotsumatsu O, McNally E, Pickart C, Ma A. Nat Immunol. 2004 Oct;5(10):1052-60. https://pubmed.ncbi.nlm.nih.gov/15334086/
Macrophage- and dendritic-cell-derived interleukin-15 receptor alpha supports homeostasis of distinct CD8+ T cell subsets. Mortier E, Advincula R, Kim L, Chmura S, Barrera J, Reizis B, Malynn BA, Ma A. Immunity. 2009 Nov 20;31(5):811-22. https://pubmed.ncbi.nlm.nih.gov/19913445/
IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. Mortier E, Woo T, Advincula R, Gozalo S, Ma A. J Exp Med. 2008 May 12;205(5):1213-25. https://pubmed.ncbi.nlm.nih.gov/18458113/
Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A. Science. 2000 Sep 29;289(5488):2350-4. https://pubmed.ncbi.nlm.nih.gov/11009421/
IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Lodolce JP, Boone DL, Chai S, Swain RE, Dassopoulos T, Trettin S, Ma A. Immunity. 1998 Nov 9(5);969-76. https://pubmed.ncbi.nlm.nih.gov/9846488/
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Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients. Zhang B, Magnaye KM, Stryker E, Moltzau-Anderson J, Porsche CE, Hertz S, McCauley KE, Smith BJ, Zydek M, Pollard KS, Ma A, El-Nachef N, Lynch SV. Sci Rep. 2024 Aug 9;14(1):18558. https://pubmed.ncbi.nlm.nih.gov/39122767/
A20 and the noncanonical NF-κB pathway are key regulators of neutrophil recruitment during fetal ontogeny. Rohwedder I, Wackerbarth LM, Heinig K, Ballweg A, Altstätter J, Ripphahn M, Nussbaum C, Salvermoser M, Bierschenk S, Straub T, Gunzer M, Schmidt-Supprian M, Kolben T, Schulz C, Ma A, Walzog B, Heinig M, Sperandio M. JCI Insight. 2023 Feb 22;8(4):e155968. https://pubmed.ncbi.nlm.nih.gov/36633909/
Intestinal inflammation alters the antigen-specific immune response to a skin commensal. Merana GR, Dwyer LR, Dhariwala MO, Weckel A, Gonzalez JR, Okoro JN, Cohen JN, Tamaki CM, Han J, Tasoff P, Palacios-Calderon Y, Ha CWY, Lynch SV, Segre JA, Kong HH, Kattah MG, Ma A, Scharschmidt TC. Cell Rep. 2022 May 31;39(9):110891. https://pubmed.ncbi.nlm.nih.gov/35649365/
Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis. Smith BJ, Piceno Y, Zydek M, Zhang B, Syriani LA, Terdiman JP, Kassam Z, Ma A, Lynch SV, Pollard KS, El-Nachef N. Sci Rep. 2022 Apr 1;12(1):5517. https://pubmed.ncbi.nlm.nih.gov/35365713/
Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage. Rusu I, Mennillo E, Bain JL, Li Z, Sun X, Ly KM, Rosli YY, Naser M, Wang Z, Advincula R, Achacoso P, Shao L, Razani B, Klein OD, Marson A, Turnbaugh JA, Turnbaugh PJ, Malynn BA, Ma A*, Kattah MG*. J Clin Invest. 2022 03 01; 132(5). https://pubmed.ncbi.nlm.nih.gov/35077396/
Nickel particles are present in Crohn's disease tissue and exacerbate intestinal inflammation in IBD susceptible mice. Matsuda H, Nibe-Shirakihara Y, Tamura A, Aonuma E, Arakawa S, Otsubo K, Nemoto Y, Nagaishi T, Tsuchiya K, Shimizu S, Ma A, Watanabe M, Uo M, Okamoto R, Oshima S. Biochem Biophys Res Commun. 2022 Feb 12;592:74-80. https://pubmed.ncbi.nlm.nih.gov/35032835/
Impact of Microdevice Geometry on Transit and Retention in the Murine Gastrointestinal Tract. Lykins WR, Hansen ME, Sun X, Advincula R, Finbloom JA, Jain AK, Zala Y, Ma A, Desai TA. ACS Biomater Sci Eng. 2023 Jun 12;9(6):2891-2901. https://pubmed.ncbi.nlm.nih.gov/33914503/
Adaptive response to inflammation contributes to sustained myelopoiesis and confers a competitive advantage in myelodysplastic syndrome HSCs. Muto T, Walker CS, Choi K, Hueneman K, Smith MA, Gul Z, Garcia-Manero G, Ma A, Zheng Y, Starczynowski DT. Nat Immunol. 2020 May;21(5):535-545. https://pubmed.ncbi.nlm.nih.gov/32313245/
A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis. Talpin A, Kattah MG, Advincula R, Fadrosh D, Lynch K, LaMere B, Fujimura KE, Nagalingam NA, Malynn BA, Lynch SV, Ma A. PLoS One. 2019; 14(7):e0218999. https://pubmed.ncbi.nlm.nih.gov/31295268/
Interleukin-17 signaling triggers degradation of the constitutive NF-κB inhibitor ABIN-1. Cruz JA, Childs EE, Amatya N, Garg AV, Beyaert R, Kane LP, Aneskievich BJ, Ma A, Gaffen SL. Immunohorizons. 2017 Sep;1(7):133-141. https://pubmed.ncbi.nlm.nih.gov/30761389/
OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination. Pasupala N, Morrow ME, Que LT, Malynn BA, Ma A, Wolberger C. J Biol Chem. 2018 Nov 23;293(47):18285-18295. https://pubmed.ncbi.nlm.nih.gov/30282802/
A20 and ABIN-1 synergistically preserve intestinal epithelial cell survival. Kattah MG, Shao L, Rosli YY, Shimizu H, Whang MI, Advincula R, Achacoso P, Shah S, Duong BH, Onizawa M, Tanbun P, Malynn BA, Ma A. J Exp Med. 2018 07 02; 215(7):1839-1852. https://pubmed.ncbi.nlm.nih.gov/29930103/
A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling. Schneider C, O'Leary CE, von Moltke J, Liang HE, Ang QY, Turnbaugh PJ, Radhakrishnan S, Pellizzon M, Ma A, Locksley RM. Cell. 2018 Jul 12;174(2):271-284.e14. https://pubmed.ncbi.nlm.nih.gov/29887373/
ABIN-1 regulates RIPK1 activation by linking Met1 ubiquitylation with Lys63 deubiquitylation in TNF-RSC. Dziedzic SA, Su Z, Jean Barrett V, Najafov A, Mookhtiar AK, Amin P, Pan H, Sun L, Zhu H, Ma A, Abbott DW, Yuan J. Nat Cell Biol. 2018 Jan;20(1):58-68. https://pubmed.ncbi.nlm.nih.gov/29203883/
Hypomorphic A20 expression confers susceptibility to psoriasis. Aki A, Nagasaki M, Malynn BA, Ma A, Kagari T. PLoS One. 2017 Jun 28;12(6):e0180481. https://pubmed.ncbi.nlm.nih.gov/28658319/
The Ubiquitin Binding Protein TAX1BP1 Mediates Autophagasome Induction and the Metabolic Transition of Activated T Cells. Whang MI, Tavares RM, Benjamin DI, Kattah MG, Advincula R, Nomura DK, Debnath J, Malynn BA, Ma A. Immunity. 2017 Mar 21;46(3):405-420. https://pubmed.ncbi.nlm.nih.gov/28314591/
Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88. Liang J, Huang HI, Benzatti FP, Karlsson AB, Zhang JJ, Youssef N, Ma A, Hale LP, Hammer GE. Cell Rep. 2016 Oct 25;17(5):1330-1343. https://pubmed.ncbi.nlm.nih.gov/27783947/
TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy. Matsuzawa Y, Oshima S, Takahara M, Maeyashiki C, Nemoto Y, Kobayashi M, Nibe Y, Nozaki K, Nagaishi T, Okamoto R, Tsuchiya K, Nakamura T, Ma A, Watanabe M. Autophagy. 2015;11(7):1052-62. https://pubmed.ncbi.nlm.nih.gov/26043155/
Planar microdevices for enhanced in vivo retention and oral bioavailability of poorly permeable drugs. Chirra HD, Shao L, Ciaccio N, Fox CB, Wade JM, Ma A, Desai TA. Adv Healthc Mater. 2014 Oct;3(10):1648-54. https://pubmed.ncbi.nlm.nih.gov/24711341/
The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation. Tiruppathi C, Soni D, Wang DM, Xue J, Singh V, Thippegowda PB, Cheppudira BP, Mishra RK, Debroy A, Qian Z, Bachmaier K, Zhao YY, Christman JW, Vogel SM, Ma A, Malik AB. Nat Immunol. 2014 Mar;15(3):239-47. https://pubmed.ncbi.nlm.nih.gov/24487321/
ABIN-1 protects against psoriasis by restricting MyD88 signals in dendritic cells. Callahan JA, Hammer GE, Agelides A, Duong BH, Oshima S, North J, Advincula R, Shifrin N, Truong HA, Paw J, Barrera J, DeFranco A, Rosenblum MD, Malynn BA, Ma A. J Immunol. 2013 Jul 15;191(2):535-9. https://pubmed.ncbi.nlm.nih.gov/23785118/
The deubiquitinase A20 mediates feedback inhibition of interleukin-17 receptor signaling. Garg AV, Ahmed M, Vallejo AN, Ma A, Gaffen SL. Sci Signal. 2013 Jun 4;6(278):ra44. https://pubmed.ncbi.nlm.nih.gov/23737552/
A20 restricts wnt signaling in intestinal epithelial cells and suppresses colon carcinogenesis. Shao L, Oshima S, Duong B, Advincula R, Barrera J, Malynn BA, Ma A. PLoS One. 2013 May 6;8(5):e62223. https://pubmed.ncbi.nlm.nih.gov/23671587/
Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation. Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, Kamei K, Ma A, Iwai K, Nureki O. EMBO J. 2012 Oct 3;31(19):3856-70. https://pubmed.ncbi.nlm.nih.gov/23032187/ Direct, noncatalytic mechanism of IKK inhibition by A20. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ. Mol Cell. 2011 Nov 18;44(4):559-71. https://pubmed.ncbi.nlm.nih.gov/22099304/ Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes. Shembade N, Ma A, Harhaj EW. Science. 2010 Feb 26;327(5969):1135-9. https://pubmed.ncbi.nlm.nih.gov/20185725/ A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response. Ashida H, Kim M, Schmidt-Supprian M, Ma A, Ogawa M, Sasakawa C. Nat Cell Biol. 2010 Jan;12(1):66-73; sup pp 1-9. https://pubmed.ncbi.nlm.nih.gov/20010814/ Cutting edge: IL-15-independent NK cell response to mouse cytomegalovirus infection. Sun JC, Ma A, Lanier LL. J Immunol. 2009 Sep 1;183(5):2911-4. https://pubmed.ncbi.nlm.nih.gov/19648279/ Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W, Shifrin N, Petri MA, Kamboh MI, Manzi S, Seldin MF, Gregersen PK, Behrens TW, Ma A, Kwok PY, Criswell LA. Nat Genet. 2008 Sep;40(9):1062-4. https://pubmed.ncbi.nlm.nih.gov/19165919/ Encoding NF-kappaB temporal control in response to TNF: distinct roles for the negative regulators IkappaBalpha and A20. Werner SL, Kearns JD, Zadorozhnaya V, Lynch C, O'Dea E, Boldin MP, Ma A, Baltimore D, Hoffmann A. Genes Dev. 2008 Aug 1;22(15):2093-101. https://pubmed.ncbi.nlm.nih.gov/18676814/ Homeostatic MyD88-dependent signals cause lethal inflammation in the absence of A20. Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, Lee B, Shifrin N, Malynn BA, Ma A. J Exp Med. 2008 Feb 18;205(2):451-64. https://pubmed.ncbi.nlm.nih.gov/18268035/ IkappaB kinase beta phosphorylates the K63 deubiquitinase A20 to cause feedback inhibition of the NF-kappaB pathway. Hutti JE, Turk BE, Asara JM, Ma A, Cantley LC, Abbott DW. Mol Cell Biol. 2007 Nov;27(21):7451-61. https://pubmed.ncbi.nlm.nih.gov/17709380/ Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis. Burkett PR, Koka R, Chien M, Chai S, Boone DL, Ma A. J Exp Med. 2004 Oct 4;200(7):825-34. https://pubmed.ncbi.nlm.nih.gov/15452177/ Cutting edge: murine dendritic cells require IL-15R alpha to prime NK cells. Koka R, Burkett P, Chien M, Chai S, Boone DL, Ma A. J Immunol. 2004 Sep 15;173(6):3594-8. https://pubmed.ncbi.nlm.nih.gov/15356102/ De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM. Nature. 2004 Aug 5;430(7000):694-9. https://pubmed.ncbi.nlm.nih.gov/15258597/ Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice. Koka R, Burkett PR, Chien M, Chai S, Chan F, Lodolce JP, Boone DL, Ma A. J Exp Med. 2003 Apr 21;197(8):977-84. https://pubmed.ncbi.nlm.nih.gov/12695489/ IL-15R alpha expression on CD8+ T cells is dispensable for T cell memory. Burkett PR, Koka R, Chien M, Chai S, Chan F, Ma A, Boone DL. Proc Natl Acad Sci USA. 2003 Apr 15;100(8):4724-9. https://pubmed.ncbi.nlm.nih.gov/12671073/ Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. Becker TC, Wherry EJ, Boone D, Murali-Krishna K, Antia R, Ma A, Ahmed R. J Exp Med. 2002 Jun 17;195(12):1541-8. https://pubmed.ncbi.nlm.nih.gov/12070282/ Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells. Schluns KS, Williams K, Ma A, Zheng XX, Lefrançois L. J Immunol. 2002 May 15;168(10):4827-31. https://pubmed.ncbi.nlm.nih.gov/11994430/