Abstract/Details

Prostaglandin D2 differentially regulates functions of human NK cell subsets through distinct receptors


2008 2008

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Abstract (summary)

Human peripheral Natural Killer (NK) cells are phenotypically identified as CD161+CD3 cells that can be divided into three subsets based on the expression of CD56: CD56, CD56low and CD56high cells. CD56low and CD56high NK cells together constitute the majority of human peripheral NK cells. These CD56+ cells produce a type-1 cytokine, IFN-γ, and play critical roles in the immune defense against tumors and virus infections. On the other hand, CD56 cells constitute a minor subpopulation of NK cells, some of which are capable of producing type-2 cytokines (IL-13 and IL-4). Type-2 cytokine producing NK cells have been suggested to participate in allergic responses. In the current work, we have demonstrated that CD56+ NK cells express a prostaglandin D2 (PGD2) receptor, D prostanoid receptor (DP). PGD2 signaling through DP suppresses cytotoxicity, cytokine production, chemotaxis and Ca2+ mobilization of CD56+ NK cells. Alternatively, a significant proportion of CD56 NK cells express another PGD2 receptor, chemoattractant receptor-like molecule on Th-2 cells (CRTH2). We have shown that the majority of type-2 cytokine producing NK cells in circulation are CRTH2+CD56 NK cells and these cells can accumulate in the allergic airways of asthmatic subjects upon allergen challenge. Our findings suggest that this chemotactic migration of CRTH2+CD56 NK cells is induced by PGD2 signaling through CRTH2. Together, these results identify novel mechanisms by which PGD2 can differentially regulate activities of NK cell subsets. The data also significantly improve the characterization of type-2 NK cells and further suggest their possible involvement in allergic diseases.

Indexing (details)


Subject
Immunology
Classification
0982: Immunology
Identifier / keyword
Health and environmental sciences, Allergies, Asthma, Natural killer cells, Prostaglandin
Title
Prostaglandin D2 differentially regulates functions of human NK cell subsets through distinct receptors
Author
Chen, Yingying
Number of pages
154
Publication year
2008
Degree date
2008
School code
0272
Source
DAI-B 73/01, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124952741
University/institution
Thomas Jefferson University
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3480610
ProQuest document ID
899273801
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/899273801
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