Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3 + Treg in the Small Intestine

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-04, Vol.28 (8), p.3366
• Main Authors: Saksida, Tamara, Paunović, Verica, Koprivica, Ivan, Mićanović, Dragica, Jevtić, Bojan, Jonić, Natalija, Stojanović, Ivana, Pejnović, Nada
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics; Antigens; Autoimmunity; B cells; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - pathology; Diet; Disease; Forkhead Transcription Factors - genetics; Foxp3 protein; gut-associated lymphoid tissue; Homeostasis; Hyperglycemia; Immunity, Innate; Immunoregulation; Insulin; Interleukin 2; Intestine; Intestine, Small - pathology; Investigations; Lamina propria; Lymphatic system; Lymphocytes; Lymphocytes - pathology; Lymphocytes T; Lymphoid cells; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Microbiota; Pathogenesis; regulatory T cells; Small intestine; Streptozocin; T-Lymphocytes, Regulatory; Transcription Factors; Type 1 diabetes; type 3 innate lymphoid cells
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28083366

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.