Clinical Laboratory Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
sliang@smail.hust.edu.cn
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Received
Accepted
Published Online
2010-04-22
2010-06-10
2010-09-05
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Abstract
The autoimmune regulator (AIRE) is a crucial factor for the induction of central tolerance, and mutations in this gene lead to abnormal immune responses. However, the role of AIRE in autophagy in immune cells, especially in monocytes, is obscure. In the present study, we found that overexpression of AIRE in THP-1 human monocytes resulted in increased endogenous light chain 3 (LC3)-II level and elevated LC3 positive vesicles. Moreover, an autophagy inhibitor or knockdown of AIRE by small interference RNA attenuated these effects. In contrast, the expression of p62/SQSTM1 remained unchanged in THP-1 cells after the corresponding treatment. Our findings indicate that AIRE plays a role in the regulation of autophagy in THP-1 human monocytes.
International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies. NotarangeloL D, FischerA, GehaR S, CasanovaJ L, ChapelH, ConleyM E, Cunningham-RundlesC, EtzioniA, HammartrömL, NonoyamaS, OchsH D, PuckJ, RoifmanC, SegerR, WedgwoodJ. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol, 2009, 124(6): 1161–1178
[2]
AndersonM S, VenanziE S, KleinL, ChenZ, BerzinsS P, TurleyS J, von BoehmerH, BronsonR, DierichA, BenoistC, MathisD. Projection of an immunological self shadow within the thymus by the aire protein. Science, 2002, 298(5597): 1395–1401
[3]
KogawaK, NagafuchiS, KatsutaH, KudohJ, TamiyaS, SakaiY, ShimizuN, HaradaM. Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol Lett, 2002, 80(3): 195–198
[4]
RamseyC, HässlerS, MaritsP, KämpeO, SurhC D, PeltonenL, WinqvistO. Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator. Eur J Immunol, 2006, 36(2): 305–317
[5]
SillanpääN, MagureanuC G, MurumägiA, ReinikainenA, WestA, ManninenA, LahtiM, RankiA, SakselaK, KrohnK, LahesmaaR, PetersonP. Autoimmune regulator induced changes in the gene expression profile of human monocyte-dendritic cell-lineage. Mol Immunol, 2004, 41(12): 1185–1198
[6]
MünzC. Enhancing immunity through autophagy. Annu Rev Immunol, 2009, 27: 423–449
[7]
AkiyoshiH, HatakeyamaS, PitkänenJ, MouriY, DoucasV, KudohJ, TsurugayaK, UchidaD, MatsushimaA, OshikawaK, NakayamaK I, ShimizuN, PetersonP, MatsumotoM. Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. J Biol Chem, 2004, 279(32): 33984–33991
[8]
KabeyaY, MizushimaN, UenoT, YamamotoA, KirisakoT, NodaT, KominamiE, OhsumiY, YoshimoriT. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J, 2000, 19(21): 5720–5728
[9]
BlommaartE F, KrauseU, SchellensJ P, Vreeling-SindelárováH, MeijerA J. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem, 1997, 243(1-2): 240–246
[10]
PankivS, ClausenT H, LamarkT, BrechA, BruunJ A, OutzenH, ØvervatnA, BjørkøyG, JohansenT. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem, 2007, 282(33): 24131–24145
González-PoloR A, BoyaP, PauleauA L, JalilA, LarochetteN, SouquèreS, EskelinenE L, PierronG, SaftigP, KroemerG. The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci, 2005, 118(Pt 14): 3091–3102
[14]
UchidaD, HatakeyamaS, MatsushimaA, HanH, IshidoS, HottaH, KudohJ, ShimizuN, DoucasV, NakayamaK I, KurodaN, MatsumotoM. AIRE functions as an E3 ubiquitin ligase. J Exp Med, 2004, 199(2): 167–172
[15]
HanadaT, NodaN N, SatomiY, IchimuraY, FujiokaY, TakaoT, InagakiF, OhsumiY. The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem, 2007, 282(52): 37298–37302
[16]
ColosettiPPuissantA, RobertG, LucianoF, JacquelA, GounonP, CassutoJ P, AubergerP. Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy, 2009, 5(8): 1092–1098
[17]
HongM, RyanK R, ArkwrightP D, GenneryA R, CostiganC, DominguezM, DenningD W, McConnellV, CantA J, AbinunM, SpickettG P, SwanD C, GillespieC S, YoungD A, LilicD. Pattern recognition receptor expression is not impaired in patients with chronic mucocutanous candidiasis with or without autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. Clin Exp Immunol, 2009, 156(1): 40–51
[18]
PerniolaR, CongedoM, RizzoA, Sticchi DamianiA, FaneschiM L, PizzolanteM, LobreglioG. Innate and adaptive immunity in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Mycoses, 2008, 51(3): 228–235
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