ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice
2021
Аутори:
Koprivica, IvanMićanović, Dragica
Saksida, Tamara
Cavalli, Eugenio
Auci, Dominick
Despotović, Sanja
Pejnović, Nada
Stošić-Grujičić, Stanislava
Nicoletti, Ferdinando
Stojanović, Ivana D.
Остала ауторства
Saksida, TamaraStanisavljević, Suzana
Miljković, Đorđe
Тип документа:
Конференцијски прилог (Објављена верзија)
,
© 2019 Institute for Biological Research "Siniša Stanković" – National Institute of Republic of Serbia, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт:
Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
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 known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
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 the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
У:
- Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia. Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia; 2019. p. 100.