Sin1 regulates Treg development but is not required for T cell growth and proliferation

Details

• Alternative Title:
  Eur J Immunol
• Personal Author:
  Chang, Xing ; Lazorchak, Adam S. ; Liu, Dou ; Su, Bing
• Description:
  Mammalian Sin1 plays key roles in the regulation of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling. Sin1 is an essential component of mTOR complex 2 (mTORC2). The functions of Sin1 and mTORC2 remain largely unknown in T cells. Here, we investigate Sin1 function in T cells using mice that lack Sin1 in the hematopoietic system. Sin1 deficiency blocks the mTORC2-dependent Akt phosphorylation in T cells during development and activation. Sin1-deficient T cells exhibit normal thymic cellularity and percentages of double-negative, double-positive, and single-positive CD4(+) and CD8(+) thymocytes. Sin1 deficiency does not impair T-cell receptor (TCR) induced growth and proliferation. Sin1 appears dispensable for in vitro CD4(+) helper cell differentiation. However, Sin1 deficiency results in an increased proportion of Foxp3(+) natural T-regulatory (nTreg) cells in the thymus. The TGF-β-dependent differentiation of CD4(+) T cells in vitro is enhanced by the inhibition of mTOR but not by loss of Sin1 function. Our results reveal that Sin1 and mTORC2 are dispensable for the development and activation of T cells but play a role in nTreg-cell differentiation.
• Subjects:
  • Animals
  • Carrier Proteins
  • Cell Differentiation
  • Cell Proliferation
  • Lymphocyte Activation
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Multiprotein Complexes
  • Proteins
  • Proto-Oncogene Proteins c-akt
  More +
• Source:
  Eur J Immunol. 42(6):1639-1647
• Pubmed ID:
  22678916
• Pubmed Central ID:
  PMC3663871
• Document Type:
  Journal Article
• Funding:
  R01 AI063348/AI/NIAID NIH HHSUnited States/ ; R01 HL070225/HL/NHLBI NIH HHSUnited States/ ; PR093728/PR/OCPHP CDC HHSUnited States/ ; AI063348/AI/NIAID NIH HHSUnited States/
• Volume:
  42
• Issue:
  6
• Download URL:
  https://stacks.cdc.gov/view/cdc/33568/cdc_33568_DS1.pdf
• File Type:
  [PDF - 1.04 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:588d17e185d94583f8e6dbd5adf000096d5abd935d4fc32f35d893e992396a05