Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Saksida T

PROVIDER: S-EPMC10141349 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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

Saksida Tamara T Paunović Verica V Koprivica Ivan I Mićanović Dragica D Jevtić Bojan B Jonić Natalija N Stojanović Ivana I Pejnović Nada N

Molecules (Basel, Switzerland) 20230411 8

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<sup>+</sup> 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 mi ...[more]

PMID: 37110604

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Project description:BackgroundImmune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL-34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8+ Tregs in a rat model of transplantation tolerance and by activated FOXP3+ CD4+ and CD8+ Tregs in human healthy individuals. However, its role in autoimmunity and potential in human diseases remains to be determined.MethodsWe generated Il34-/- rats and using both Il34-/- rats and mice, we investigated their phenotype under inflammatory conditions. Using Il34-/- rats, we further analyzed the impact of the absence of expression of IL-34 for CD4+ Tregs suppressive function. We investigated the potential of IL-34 in human disease to prevent xenogeneic GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, taking advantage of a biocollection, we investigated the correlation between presence of IL-34 in the serum and kidney transplant rejection.ResultsHere we report that the absence of expression of IL-34 in Il34-/- rats and mice leads to an unstable immune phenotype, with production of multiple auto-antibodies, exacerbated under inflammatory conditions with increased susceptibility to DSS- and TNBS-colitis in Il34-/- animals. Moreover, we revealed the striking inability of Il34-/- CD4+ Tregs to protect Il2rg-/- rats from a wasting disease induced by transfer of pathogenic cells, in contrast to Il34+/+ CD4+ Tregs. We also showed that IL-34 treatment delayed EAE in mice as well as GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, we show that presence of IL-34 in the serum is associated with a longer rejection-free period in kidney transplanted patients.ConclusionAltogether, our data emphasize on the crucial necessity of IL-34 for immune homeostasis and for CD4+ Tregs suppressive function. Our data also shows the therapeutic potential of IL-34 in human transplantation and auto-immunity.Highlights-Absence of expression of IL-34 in Il34-/- rats and mice leads to an unstable immune phenotype, with a production of multiple auto-antibodies and exacerbated immune pathology under inflammatory conditions. -Il34-/- CD4+ Tregs are unable to protect Il2rg-/- rats from colitis induced by transfer of pathogenic cells. -IL-34 treatment delayed EAE in mice, as well as acute GVHD and human skin allograft rejection in immune-humanized immunodeficient NSG mice.

Dataset Information

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

Publications

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

Similar Datasets

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Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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