@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response
causes the death of pancreatic β-cells. Attempts to induce anti-inflammatory/regulatory
immune mechanisms that would attenuate disease progression have shown little or no
beneficial effects. We introduced microparticles (MPs) loaded with Transforming Growth
Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA), both well-known stimulators of T
regulatory cell (Treg) differentiation and stabilization. Male C57BL/6 mice were treated
with multiple low doses of streptozotocin for T1D induction, and with vehicle, empty MPs,
or ATRA- and TGF-β-loaded MPs for 10 days (every other day). Both T1D incidence and
immune cell infiltration into the pancreatic islets was lower in ATRA/TGF-β-treated mice.
In Peyer’s patches (PP), ATRA/TGF-β up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β e xpression was r educed i n P P, a s w as t he r atio o f i NOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by a
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower, and was accompanied by down-regulation in
RORγt expression (key transcription factor of IL-17). The situation in the pancreatic
lymph nodes (PLN) was similar to PP regarding the down-regulation of Th1 cells.
Additionally, in response to ATRA/TGF-β treatment, the proliferation of T effector cells
was reduced in PLN, while Treg proliferated more, and several crucial markers of Treg
suppressive activity were increased. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg responses and inhibition of
Th1 cell differentiation in the draining lymph nodes, thus blocking the entrance of immune
cells into the pancreatic islets and protecting β-cells from further destruction.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.",
title = "Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles",
pages = "113",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5778"
}
