Human amylin induces CD4+Foxp3+ regulatory T cells in the protection from autoimmune diabetes.
Immunol Res
; 66(1): 179-186, 2018 02.
Article
de En
| MEDLINE
| ID: mdl-28983871
ABSTRACT
Autoimmune diabetes is a disorder of immune homeostasis that leads to targeted insulin-secreting islet ß cell destruction characterized by insulitis. Human amylin (hA) is an important neuroendocrine hormone co-secreted with insulin by pancreatic ß cells. Here, we report hA immune-modulatory action through inducing regulatory T cells. We ex vivo-treated human peripheral blood mononuclear cells (hPBMCs) with hA for 24 h and counted CD4+Foxp3+ regulatory T cells (Treg) using flow cytometry. Diabetic status was monitored and splenic Treg were measured in non-obese diabetic (NOD) male mice. NOD mice were intraperitoneally injected once daily with hA (n = 25) or solvent for control (n = 25) for 7 months continuously. Spleen tissues were collected at the end of intervention and processed for flow cytometry and Western blot. We found a 2.9-fold (p < 0.05) increase of CD4+Foxp3+ Treg in hPBMCs treated with 10 nmol/L hA compared with negative control. Incidence of diabetes in hA-treated NOD mice decreased 44% (p = 0.045) in the 6th month and 57% (p = 0.0002) in the 7th month. Meanwhile, the hA treatment induced a 1.5-fold increase of CD4+Foxp3+ Treg from mouse splenocytes (p = 0.0013). Expression of transforming growth factor-ß (TGF-ß) and toll-like receptor-4 (TLR-4) were upregulated in hA-treated mice. Human amylin might protect against autoimmune diabetes via the induction of CD4+Foxp3+ Treg, which suggests a novel approach to improve autoimmune conditions.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes T régulateurs
/
Diabète de type 1
/
Cellules à insuline
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Polypeptide amyloïde des ilots
Limites:
Animals
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Humans
/
Male
Langue:
En
Journal:
Immunol Res
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2018
Type de document:
Article
Pays d'affiliation:
Chine