The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice
2019
Autori:
Jevtić, BojanSaksida, Tamara
Mićanović, Dragica
Koprivica, Ivan
Paunović, Verica
Stojanović, Ivana D.
Pejnović, Nada
Ostala autorstva
Saksida, TamaraStanisavljević, Suzana
Miljković, Đorđe
Tip dokumenta:
Konferencijski prilog (Objavljena verzija)
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© 2019 Institute for Biological Research "Siniša Stanković" – National Institute of Republic of Serbia, University of Belgrade
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the imbalance
between the CD4 or CD8 T effector (Teff) cells and the FoxP3+CD4 T regulatory cells
(Tregs) that leads to pancreatic beta-cells destruction causing insulin deficiency.
Environmental factors, diet and microbiome are associated with the recent rise in T1D
incidence. Intestinal immune cells must maintain a tolerogenic response in the gut that
involves the development of Tregs. Recent data show that IL-2-producing type 3 innate
lymphoid cells ILC3s (IL-2+ILC3) in the small intestine are essential for maintaining
FoxP3+ Tregs and oral tolerance to dietary antigens and reveal the previously unknown
direct communication between ILC3s and Treg cells in the gut. We investigated the
frequencies of small intestine lamina propria IL-2+ILC3s and FoxP3+ Tregs during
transition from prediabetes to diabetes in young and old female NOD mice. 20 weeks
old, diabetic NOD mice had higher frequencies of LinnegCD45+RORγt+CD127+ ILC3s
in small intestine lamina propria compared to 4 weeks of age-young NOD mice.
However, the frequencies of IL-2-producing ILC3s and CD4+CD25hiFoxP3+ Tregs
were significantly lower in diabetic NOD mice compared to young, prediabetic mice.
We next investigated how microbiota change before diabetes induction is reflected on
Treg and ILC3 populations. Male C57BL/6 mice were treated with broad spectrum
antibiotics (ABX) for 14 days and then T1D was induced by multiple low doses of
streptozotocin (STZ). Ex vivo cell analyses was done on day 10 after the first STZ
injection. The significantly higher incidence of T1D observed in ABX-treated mice
correlated with significantly lower frequencies of IL-2-producing ILC3s and
FoxP3+Tregs in small intestine lamina propria compared to mice treated with STZ only.
The obtained findings show that the decrease of tolerogenic ILC3s and FoxP3+Tregs in
small intestine is associated with the progression and higher incidence of T1D.
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
U:
- 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. 102.