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Temporal regulation of intracellular organelle homeostasis in T lymphocytes by autophagy.

Publication ,  Journal Article
Jia, W; He, Y-W
Published in: J Immunol
May 1, 2011

The highly conserved self-degradation pathway known as autophagy plays important roles in regulating T lymphocyte homeostasis. Recently, we found that T lymphocytes lacking the autophagy-related gene Atg5 or Atg7 have defective survival and contain expanded mitochondria and endoplasmic reticulum (ER); however, whether these defects are caused by impaired autophagy or by defects in their autophagy-independent signaling capacity of Atg5 or Atg7 in T lymphocytes remains unknown. Furthermore, the function of the microtubule-associated protein L chain 3 (LC3) conjugation system in T lymphocytes remains unclear. To address these questions, we generated conditional knockout mice with specific deletion of Atg3, a ubiquitin enzyme E2-like molecule involved in the LC3 conjugation system, in T lymphocytes. Atg3-deficient T lymphocytes displayed a phenotype similar to those of Atg7- and Atg5-deficient T cells. The survival of Atg3-deficient naive CD4(+) and CD8(+) T cells was defective. Furthermore, the mitochondria and ER were expanded in Atg3-deficient T cells. Interestingly, mitochondrial and ER content did not change instantly upon inducible deletion of Atg3 in mature T lymphocytes in vitro. Instead, it began to expand 10 d after inducible deletion of Atg3 in mature T lymphocytes, and mitochondrial content continued to increase on day 18. Cell death began to increase 24 d after inducible deletion of Atg3. These data show that the LC3 conjugation system is essential for autophagy in T lymphocytes. Our data suggest that autophagy promotes T lymphocyte survival by regulating organelle homeostasis and that the decreased survival of autophagy-deficient T cells is due to the temporal accumulation of these autophagy-related defects.

Duke Scholars

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

May 1, 2011

Volume

186

Issue

9

Start / End Page

5313 / 5322

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Reverse Transcriptase Polymerase Chain Reaction
  • Organelles
  • Microtubule-Associated Proteins
  • Microscopy, Electron, Transmission
  • Mice, Knockout
  • Mice
  • Male
  • Immunology
  • Homeostasis
 

Citation

APA
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MLA
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Jia, W., & He, Y.-W. (2011). Temporal regulation of intracellular organelle homeostasis in T lymphocytes by autophagy. J Immunol, 186(9), 5313–5322. https://doi.org/10.4049/jimmunol.1002404
Jia, Wei, and You-Wen He. “Temporal regulation of intracellular organelle homeostasis in T lymphocytes by autophagy.J Immunol 186, no. 9 (May 1, 2011): 5313–22. https://doi.org/10.4049/jimmunol.1002404.
Jia, Wei, and You-Wen He. “Temporal regulation of intracellular organelle homeostasis in T lymphocytes by autophagy.J Immunol, vol. 186, no. 9, May 2011, pp. 5313–22. Pubmed, doi:10.4049/jimmunol.1002404.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

May 1, 2011

Volume

186

Issue

9

Start / End Page

5313 / 5322

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Reverse Transcriptase Polymerase Chain Reaction
  • Organelles
  • Microtubule-Associated Proteins
  • Microscopy, Electron, Transmission
  • Mice, Knockout
  • Mice
  • Male
  • Immunology
  • Homeostasis