Unique Features of Pancreatic-Resident Regulatory T Cells in Autoimmune Type 1 Diabetes

Abstract

Recent progress in regulatory T cells (Tregs) biology emphasizes the importance of understanding tissue-resident Tregs in response to tissue-specific environment. Now, emerging evidence suggests that pancreatic-resident forkhead box P3+ Tregs have distinguishable effects on the suppression of over-exuberant immune responses in autoimmune type 1 diabetes (T1D). Thus, there is growing interest in elucidating the role of pancreatic-resident Tregs that function and evolve in the local environment. In this review, we discuss the phenotype and function of Tregs residing in pancreatic tissues and pancreatic lymph nodes, with emphasis on the unique subpopulations of Tregs that control the disease progression in the context of T1D. Specifically, we discuss known and possible modulators that influence the survival, migration, and maintenance of pancreatic Tregs.

Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes

“…The Treg accumulation pattern in the pancreas or PLN is governed by the expression of various adhesion molecules, chemokine ligands, and their respective integrins or chemokine receptors on the Tregs 38 . Studies have shown decreased expression of CXCL12 in the PLN correlated with the lack of Tregs in diabetic NOD mice 8 .…”

Type 1 diabetes and engineering enhanced islet transplantation

“…They are a subset for CD4 + cells that originate from the thymus and are identified by intracellular FoxP3 or the surface marker CD25. Tregs are responsible for preventing autoimmunity and stopping the immune response to foreign organisms [194] , [195] , [196] . Tregs/islet co-transplantation increased islet survival compared to islets transplanted alone [197] .…”

Means, Motive, and Opportunity: Do Non-Islet-Reactive Infiltrating T Cells Contribute to Autoimmunity in Type 1 Diabetes?

“…CD20 + B cells, macrophages and other immune cells are also present in insulitis or in peri-insulitis. Their presence and numbers are associated with length of disease and age at disease diagnosis (18)(19)(20)(34)(35)(36)(37). Only a few studies have attempted to identify CD4 + regulatory T cells (Tregs) in the human pancreas with some success (38), but other studies did not confirm the presence of conventional CD4 + Tregs in human insulitis (18,20).…”