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Paracrine co-delivery of TGF-β and IL-2 using CD4-targeted nanoparticles for induction and maintenance of regulatory T cells.
- Source :
-
Biomaterials . Aug2015, Vol. 59, p172-181. 10p. - Publication Year :
- 2015
-
Abstract
- The cytokine milieu is critical for orchestration of lineage development towards effector T cell (Teff) or regulatory T cell (Treg) subsets implicated in the progression of cancer and autoimmune disease. Importantly, the fitness and survival of the Treg subset is dependent on the cytokines Interleukin-2 (IL-2) and transforming growth factor beta (TGF-β). The production of these cytokines is impaired in autoimmunity increasing the probability of Treg conversion to aggressive effector cells in a proinflammatory microenvironment. Therapy using soluble TGF-β and IL-2 administration is hindered by the cytokines' toxic pleiotropic effects and hence bioavailability to CD4 + T cell targets. Thus, there is a clear need for a strategy that rectifies the cytokine milieu in autoimmunity and inflammation leading to enhanced Treg stability, frequency and number. Here we show that inert biodegradable nanoparticles (NP) loaded with TGF-β and IL-2 and targeted to CD4 + cells can induce CD4 + Tregs in-vitro and expand their number in-vivo . The stability of induced Tregs with cytokine-loaded NP was enhanced leading to retention of their suppressive phenotype even in the presence of proinflammatory cytokines. Our results highlight the importance of a nanocarrier-based approach for stabilizing and expanding Tregs essential for cell-immunotherapy of inflammation and autoimmune disease. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01429612
- Volume :
- 59
- Database :
- Academic Search Index
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 102786351
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2015.04.003