TSG-6 produced by hMSCs delays the onset of autoimmune diabetes by suppressing Th1 development and enhancing tolerogenicity.
Genetic and immunological screening for type 1 diabetes has led to the possibility of preventing disease in susceptible individuals. Here, we show that human mesenchymal stem/stromal cells (hMSCs) and tumor necrosis factor-α-stimulated gene 6 (TSG-6), a protein produced by hMSCs in response to signals from injured tissues, delayed the onset of spontaneous autoimmune diabetes in NOD mice by inhibiting insulitis and augmenting regulatory T cells (Tregs) within the pancreas. Importantly, hMSCs with a knockdown of tsg-6 were ineffective at delaying insulitis and the onset of diabetes in mice. TSG-6 inhibited the activation of both T cells and antigen-presenting cells (APCs) in a CD44-dependent manner. Moreover, multiple treatments of TSG-6 rendered APCs more tolerogenic, capable of enhancing Treg generation and delaying diabetes in an adoptive transfer model. Therefore, these results could provide the basis for a novel therapy for the prevention of type 1 diabetes.
Texas A&M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott & White, Temple, Texas, USA.
Daniel J
DJ
Kota
Lindsey L
LL
Wiggins
Nara
N
Yoon
Ryang Hwa
RH
Lee
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*
D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human