Skip to main content
SpringerLink
Log in

Autoimmune regulator regulates autophagy in THP-1 human monocytes

  • Research Article
  • Published:
Frontiers of Medicine in China Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies. Notarangelo L D, Fischer A, Geha R S, Casanova J L, Chapel H, Conley M E, Cunningham-Rundles C, Etzioni A, Hammartröm L, Nonoyama S, Ochs H D, Puck J, Roifman C, Seger R, Wedgwood J. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol, 2009, 124(6): 1161–1178

    Article  CAS  PubMed  Google Scholar 

  2. Anderson M S, Venanzi E S, Klein L, Chen Z, Berzins S P, Turley S J, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D. Projection of an immunological self shadow within the thymus by the aire protein. Science, 2002, 298(5597): 1395–1401

    Article  CAS  PubMed  Google Scholar 

  3. Kogawa K, Nagafuchi S, Katsuta H, Kudoh J, Tamiya S, Sakai Y, Shimizu N, Harada M. Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol Lett, 2002, 80(3): 195–198

    Article  CAS  PubMed  Google Scholar 

  4. Ramsey C, Hässler S, Marits P, Kämpe O, Surh C D, Peltonen L, Winqvist O. Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator. Eur J Immunol, 2006, 36(2): 305–317

    Article  CAS  PubMed  Google Scholar 

  5. Sillanpää N, Magureanu C G, Murumägi A, Reinikainen A, West A, Manninen A, Lahti M, Ranki A, Saksela K, Krohn K, Lahesmaa R, Peterson P. Autoimmune regulator induced changes in the gene expression profile of human monocyte-dendritic cell-lineage. Mol Immunol, 2004, 41(12): 1185–1198

    Article  PubMed  Google Scholar 

  6. Münz C. Enhancing immunity through autophagy. Annu Rev Immunol, 2009, 27: 423–449

    Article  PubMed  Google Scholar 

  7. Akiyoshi H, Hatakeyama S, Pitkänen J, Mouri Y, Doucas V, Kudoh J, Tsurugaya K, Uchida D, Matsushima A, Oshikawa K, Nakayama K I, Shimizu N, Peterson P, Matsumoto M. Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. J Biol Chem, 2004, 279(32): 33984–33991

    Article  CAS  PubMed  Google Scholar 

  8. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J, 2000, 19(21): 5720–5728

    Article  CAS  PubMed  Google Scholar 

  9. Blommaart E F, Krause U, Schellens J P, Vreeling-Sindelárová H, Meijer A J. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem, 1997, 243(1–2): 240–246

    Article  CAS  PubMed  Google Scholar 

  10. Pankiv S, Clausen T H, Lamark T, Brech A, Bruun J A, Outzen H, Øvervatn A, Bjørkøy G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem, 2007, 282(33): 24131–24145

    Article  CAS  PubMed  Google Scholar 

  11. Bjørkøy G, Lamark T, Pankiv S, Øvervatn A, Brech A, Johansen T. Monitoring autophagic degradation of p62/SQSTM1. Methods Enzymol, 2009, 452: 181–197

    Article  PubMed  Google Scholar 

  12. Gray D, Abramson J, Benoist C, Mathis D. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med, 2007, 204(11): 2521–2528

    Article  CAS  PubMed  Google Scholar 

  13. González-Polo R A, Boya P, Pauleau A L, Jalil A, Larochette N, Souquère S, Eskelinen E L, Pierron G, Saftig P, Kroemer G. The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci, 2005, 118(Pt 14): 3091–3102

    Article  PubMed  Google Scholar 

  14. Uchida D, Hatakeyama S, Matsushima A, Han H, Ishido S, Hotta H, Kudoh J, Shimizu N, Doucas V, Nakayama K I, Kuroda N, Matsumoto M. AIRE functions as an E3 ubiquitin ligase. J Exp Med, 2004, 199(2): 167–172

    Article  CAS  PubMed  Google Scholar 

  15. Hanada T, Noda N N, Satomi Y, Ichimura Y, Fujioka Y, Takao T, Inagaki F, Ohsumi Y. The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem, 2007, 282(52): 37298–37302

    Article  CAS  PubMed  Google Scholar 

  16. Colosetti P Puissant A, Robert G, Luciano F, Jacquel A, Gounon P, Cassuto J P, Auberger P. Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy, 2009, 5(8): 1092–1098

    Article  CAS  PubMed  Google Scholar 

  17. Hong M, Ryan K R, Arkwright P D, Gennery A R, Costigan C, Dominguez M, Denning D W, McConnell V, Cant A J, Abinun M, Spickett G P, Swan D C, Gillespie C S, Young D A, Lilic D. 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

    Article  CAS  PubMed  Google Scholar 

  18. Perniola R, Congedo M, Rizzo A, Sticchi Damiani A, Faneschi M L, Pizzolante M, Lobreglio G. Innate and adaptive immunity in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Mycoses, 2008, 51(3): 228–235

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Laboratory Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Liang Shi, Li-Hua Hu & Yi-Rong Li

Authors
  1. Liang Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li-Hua Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi-Rong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li-Hua Hu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, L., Hu, LH. & Li, YR. Autoimmune regulator regulates autophagy in THP-1 human monocytes. Front. Med. China 4, 336–341 (2010). https://doi.org/10.1007/s11684-010-0096-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-010-0096-4

Keywords

Search

Navigation