Identification of Differentially Expressed Genes in Pancreatic Regulatory T-Cell SurvivalJake Carrion# and Michael Carrion#*
Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT, 06510, USA
- *Corresponding Author:
- Michael Carrion
The Anlyan Center, 300 Cedar Street
New Haven, CT, 06510, USA
E-mail: [email protected]
Received date: August 19, 2015; Accepted date: October 02, 2015; Published date: October 06, 2015
Citation: Carrion J, Carrion M (2015) Identification of Differentially Expressed Genes in Pancreatic Regulatory T-Cell Survival. J Diabetes Metab 6:612. doi:10.4172/2155-6156.1000612
Copyright: © 2015 Carrion J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Many current Diabetes treatments cause broad-based
, though future organspecific therapies may be developed by exploiting genotypic differences found in regulatory T cell (Treg) subpopulations. This study goaled to determine genes preferentially expressed in pancreatic Tregs relative to other Treg subpopulations, tissues, and immune cells to serve as targets in Diabetes therapy. Methods: Multi-step microarray analysis using GenePattern Software identified genes specific to pancreatic Tregs relative to Tregs in other tissues and to other immune-cell populations. Functional analysis of identified genes was performed using BioGrid and String Databases. Microarray datasets (n=2236) curated from the NCBI GEO database were processed (via RMA normalization, outlier-array exclusion, and global median transformation) to confirm the specificity of these genes to the pancreas, while further microarray comparisons (in R programming language via Mas-5 normalization, log2 transformation, and “trimmed mean” algorithm) were performed to confirm the link of the identified genes to diabetes
. Results: Initial microarray analysis identified genes specific to pancreatic Tregs, with the top three genes (Clps, Pnliprp1, and Pla2g1b) expressed at values 23x, 12x, and 7x higher in pancreatic Tregs than in other Treg subpopulations (p<0.05). Further analysis revealed that the pancreatic gene expression of the identified genes was almost triple that of other tissues (n=29), while comparisons among other immune-cell types indicated that these genes were expressed 32x, 12.8x, and 7.5x higher, respectively, in pancreatic Tregs than in other immune cell-types, eliminating the possibility of augmenting the autoimmune response in future treatments. Diabetic vs. nondiabetic microarray analysis confirmed the link of these genes to Type 1, but not Type 2, Diabetes. Conclusions: Future
therapies should target these genes to solely regulate pancreatic Treg levels, avoiding the broad-based immunosuppression caused by current therapies. However, gene knockout studies should be performed to further validate the functionality of the identified genes.