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Progranulin promotes tumour necrosis factor-induced proliferation of suppressive mouse CD4+ Foxp3+ regulatory T cells
Hu Y.1,2; Xiao H.1; Shi T.1; Oppenheim J.J.1; Chen X.1,3
2014
Source PublicationImmunology
ISSN13652567 00192805
Volume142Issue:2Pages:193-201
Abstract

Progranulin (PGRN) is a pleiotropic growth factor with immunosuppressive properties. Recently, it was reported that PGRN was an antagonist of tumour necrosis factor (TNF) receptors, preferentially for TNFR2. However, we and others showed that TNF-TNFR2 interaction was critical for the activation and expansion of functional CD4 Foxp3 regulatory T (Treg) cells. We therefore examined the effect of PGRN on the proliferation of naturally occurring murine suppressive Treg cells induced by TNF. Consistent with our previous reports, TNF overcame the hyporesponsiveness of highly purified Treg cells to T-cell receptor stimulation. Furthermore, in the presence of interleukin-2, TNF preferentially stimulated proliferation of Treg cells contained in unfractionated CD4 cells. These effects of TNF on suppressive Treg cells were markedly increased by exogenous PGRN. TNF and TNFR2 interactions are required for this effect of PGRN, because the PGRN by itself did not stimulate Treg cell proliferation. The effect of PGRN on Treg cells was abrogated by antibody against TNFR2, and Treg cells deficient in TNFR2 also failed to respond to PGRN. Furthermore, PGRN also enhanced the proliferative responses of effector T cells to TNF, but to a lesser extent than that of Treg cells, presumably caused by the different levels of TNFR2 expression on these two subsets of CD4 cells. Hence, our data clearly show that PGRN promotes, rather than inhibits, the functional consequence of TNF-TNFR2 interaction on Treg cells. © 2014. This article is a U.S. Government work and is in the public domain in the USA.

KeywordProgranulin Proliferation Regulatory t Cells Tumour Necrosis Factor Tumour Necrosis Factor Receptor Type 2
DOI10.1111/imm.12241
URLView the original
Indexed BySCI
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000337536000004
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Cited Times [WOS]:21   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Laboratory of Molecular Immunoregulation,Cancer Inflammation Program, Center forCancer Research, National Cancer Institute,Frederick, MD, USA
2.School of Medicine,Yangtze University, Jingzhou, Hubei, China
3.Basic Science Program, Leidos Biomedi-cal Research, Inc., Frederick National Labora-tory for Cancer Research, Frederick, MD, USA
Recommended Citation
GB/T 7714
Hu Y.,Xiao H.,Shi T.,et al. Progranulin promotes tumour necrosis factor-induced proliferation of suppressive mouse CD4+ Foxp3+ regulatory T cells[J]. Immunology,2014,142(2):193-201.
APA Hu Y.,Xiao H.,Shi T.,Oppenheim J.J.,&Chen X..(2014).Progranulin promotes tumour necrosis factor-induced proliferation of suppressive mouse CD4+ Foxp3+ regulatory T cells.Immunology,142(2),193-201.
MLA Hu Y.,et al."Progranulin promotes tumour necrosis factor-induced proliferation of suppressive mouse CD4+ Foxp3+ regulatory T cells".Immunology 142.2(2014):193-201.
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