Description
- Abstract:
- The invasion of foreign pathogens and the development of cancerous cells result in human infections and diseases. The severity of this outcome is dependent on how well the immune system recognizes and responds to foreign pathogens, viruses, and cancer. As part of the innate immune system, natural killer (NK) cells provide immediate and nonspecific protection against tumors and viral infection. The balance between activating and inhibitory receptors dictates the course of NK cell action. The inhibitory killer cell lectin-like receptor G1 (KLRG1) was identified to interact with non-MHC molecules, epithelial (E-), neural (N-), and retinal (R-)cadherin. This thesis provides an in-depth characterization of KLRG1 and cadherin interaction, and offers novel insights on the bidirectional signaling induced by KLRG1/cadherin interactions to differentially regulate not only KLRG1+ cells, but also cadherin-expressing cells. Additionally, it was previously shown that upon KLRG1 stimulation, the SH2-containing inositol phosphatase-1 (SHIP-1) is recruited to the receptor. Downstream signaling molecules have been shown to influence NK cell development and differentiation into functionally distinct subsets. This raises the question of whether or not SHIP-1 influences NK cell development and maturation. Using mixed bone marrow chimera studies, we show that NK cells lacking SHIP-1 display deficiencies in maturation. This demonstrates a direct effect of SHIP-1 in promoting NK cell differentiation into mature subsets. Overall, these findings advance our understanding of the immunoregulatory functions involved in the interaction between KLRG1/cadherin as well as how SHIP-1 regulates NK cell development and differentiation.
- Notes:
- Thesis (Ph.D. -- Brown University (2012)
Access Conditions
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- In Copyright
- Restrictions on Use
- Collection is open for research.
Citation
Banh, Cindy,
"Immunoregulatory functions of KLRG1 and its associated phosphatases"
(2012).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0HM56QQ
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....