The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and Differentiation.

Abstract

The microtubule-associated protein lissencephaly 1 (Lis1) is a key regulator of cell division during stem cell renewal and differentiation. In this study, we examined the role of Lis1 in T lymphocyte homeostasis and fate diversification in response to microbial infection. T cell-specific deletion of Lis1 resulted in depletion of the peripheral CD4(+) and CD8(+) T lymphocyte pool owing to a loss of homeostatic, cytokine-induced proliferation. In contrast, cognate Ag-triggered proliferation was much less affected, enabling Lis1-deficient CD8(+) T cells to differentiate into terminal effector cells in response to microbial infection. Strikingly, however, the specification of Lis1-deficient long-lived memory CD8(+) T lymphocytes was impaired due, in part, to an apparent failure to differentiate appropriately to IL-15. Taken together, these findings suggest that Lis1 plays an important role in T cell homeostasis and the generation of memory T lymphocytes.

• Authors: Soo M Ngoi, Justine M Lopez, John T Chang
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 196 Issue 10 Pg. 4237-45 (05 15 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 27029586 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Chemical References

• Interleukin-15
• Interleukin-7
• Microtubule-Associated Proteins
• 1-Alkyl-2-acetylglycerophosphocholine Esterase
• Pafah1b1 protein, mouse

Topics

• 1-Alkyl-2-acetylglycerophosphocholine Esterase (genetics, immunology)
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Differentiation (immunology)
• Cell Division
• Homeostasis (immunology)
• Immunologic Memory
• Immunophenotyping
• Interleukin-15 (immunology)
• Interleukin-7 (immunology)
• Listeria monocytogenes
• Listeriosis (immunology)
• Lymphocyte Activation
• Mice
• Mice, Knockout
• Microtubule-Associated Proteins (genetics, immunology)
• Signal Transduction
• Thymus Gland (immunology)