Induction of regulatory T cells in the gut associated lymphoid tissues (GALT) to restore tolerance towards pancreas associated antigens

This abstract has open access
Abstract Summary

Background: Induction of Tregs in the gut can promote tolerance towards pancreas associated antigens in type 1 diabetes. In this study, we induced colonic Tregs (cTregs) by administering sodium butyrate in NOD mice and analyzed their migratory potential towards pancreas and pancreatic lymph nodes (PLN).

Methods: Female NOD mice were administered sodium butyrate (150mM) orally at 4 weeks of age (early-intervention group) and after the onset of hyperglycemia (treatment group). Tregs were isolated from colon, peripheral blood, spleen, mesenteric lymph nodes (MLN), peyer’s patches (PPs), PLN and characterized by flow cytometry. Expression of chemokines, CXCL10, CCL4, CCL5, MadCAM1, CXCL12, CCL19, and CCL22 was assessed in the pancreas by quantitative real-time RT-PCR.

Results:  The treatment group (mean±SEM, 464.5±37.6 mg/dL, n=21) showed lesser increase in hyperglycemia until 6 weeks, versus the untreated group (controls) (mean±SEM, 830.64±79.6 mg/dL, n=14) (p=0.007). Butyrate treatment also prolonged the survival of treatment              group (24 weeks, n=21) versus controls (13weeks, n=14) (p=0.04) with mild reduction in insulitis and preservation of insulin containing residual beta cells. However, the early-intervention group did not show any improvement in blood glucose levels or survival. Butyrate administration augmented the frequency of cTregs in the treatment (n=9,P=0.05) and early-intervention (n=9,P=0.01) groups. Butyrate treatment also increased Treg frequencies in MLN, PPs, and PLN but not in peripheral blood or spleen. The expression of gut-homing receptor, ?4?7 on cTregs and Tregs in PLN was increased in the treatment group suggestive of their improved migratory ability. Analysis of chemokines involved in T cell trafficking revealed higher expression of CXCL12 (p<0.003) in the pancreas of the treatment group.

Conclusions: Sodium butyrate may be useful in suppression of diabetes in NOD mice. However, further analysis of effector molecules and chemokine receptors would provide a better picture of the role of induced cTregs in restoring tolerance towards pancreas associated antigens.

Submission ID :
IDS4295
Submission Type
Abstract Topics
Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Experimental Animal Facility, Institute of Microbial Technology (IMTech), Chandigarh, India
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Abstracts With Same Type

Submission ID
Submission Title
Submission Topic
Submission Type
Primary Author
3 visits

KEY DATES

Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

Early registration deadline:
Monday 3 September 2018

Registration deadline:
Monday 15 October 2018

Contact
British Society for Immunology
+44 (0)20 3019 5901
congress@immunology.org