uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell-expressed FasL
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
Show others and affiliations
2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 117, no 20, 5381-5390 p.Article in journal (Refereed) Published
Abstract [en]

Myeloid-derived suppressor cells (MDSCs) inhibit adaptive and innate immunity and accumulate in the blood of persons with cancer, chronic inflammation, trauma, infection, and stress. Some of the factors inducing their accumulation are known; however, mechanisms regulating their turnover have not been identified. Mass spectrometry showed prominent expression of apoptosis pathway proteins, suggesting that MDSC turnover may be regulated by Fas-FasL-mediated apoptosis. This hypothesis was confirmed by showing that blood MDSCs induced by 3 mouse tumors were Fas(+) and apoptosed in response to Fas agonist in vitro and to activated FasL(+) T cells in vivo. FasL-deficient mice contained significantly more blood MDSCs than FasL(+/+) mice, and after removal of primary tumors MDSCs regressed in STAT6(-/-) and CD1(-/-) mice but not in STAT6(-/-)FasL(-/-) or CD1(-/-) FasL(-/-) mice. Fas(+) macrophages and dendritic cells did not apoptose in response to activated T cells, indicating that Fas-FasL regulation of myeloid cells was restricted to MDSCs. These results identify a new mechanism regulating MDSC levels in vivo and show a retaliatory relationship between T cells and MDSCs in that MDSCs suppress T-cell activation; however, once activated, T cells mediate MDSC apoptosis.

Place, publisher, year, edition, pages
2011. Vol. 117, no 20, 5381-5390 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-154619DOI: 10.1182/blood-2010-11-321752ISI: 000290751300017PubMedID: 21450901OAI: oai:DiVA.org:uu-154619DiVA: diva2:421316
Available from: 2011-06-08 Created: 2011-06-08 Last updated: 2011-06-08Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Analytical Chemistry
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 400 hits
ReferencesLink to record
Permanent link

Direct link