Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine
2023
Authors:
Saksida, TamaraPaunović, Verica
Koprivica, Ivan
Mićanović, Dragica
Jevtić, Bojan
Jonić, Natalija
Stojanović, Ivana D.
Pejnović, Nada
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Recent data indicate the link between the number and function of T regulatory cells (Treg)
in the gut immune tissue and initiation and development of autoimmunity associated with type
1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for
maintaining FoxP3+ Treg and there are no data about the possible role of ILC3 in T1D pathogenesis,
the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic
NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria
(SILP) compared to prediabetic NOD mice. Similarly, in multiple low doses of streptozotocin (MLDS)-
induced T1D in C57BL/6 mice, hyperglycemic mice exhibited lower numbers of ILC3, IL-2+ ILC3
and Treg in SILP compared to healthy controls. To boost T1D severity, mice were treated with
broad-spectrum antibiotics (ABX) for 14 days prior to T1D induction by MLDS. The higher incidence
of T1D in ABX-treated mice was associated with significantly lower frequencies of IL-2+ ILC3 and
FoxP3+ Treg in SILP compared with mice without ABX treatment. The obtained findings show that
the lower proportions of IL-2-expressing ILC3 and FoxP3+ Treg in SILP coincided with diabetes
progression and severity.
Keywords:
type 1 diabetes; type 3 innate lymphoid cells; regulatory T cells; interleukin-2; gut-associated lymphoid tissue; lamina propriaSource:
Molecules, 2023, 28, 8, 3366-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Serbian Clinical Immunology Fund New Castle, UK.
DOI: 10.3390/molecules28083366
ISSN: 1420-3049
PubMed: 37110604