Title: Obesity Potentiates TH2 Immunopathology Via Dysregulation of PPARg

Accession Number: GSE189216

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE189216

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Genome binding/occupancy profiling by high throughput sequencing

Organism(s): Mus musculus

Summary: Clinically, obesity is strongly associated with severe TH2 immunopathology, though the physiological, cellular, and molecular underpinnings of this association remain obscure. We demonstrate that obese mice are susceptible to severe atopic dermatitis (AD), a major manifestation of TH2 immunopathology and disease burden in humans. Mechanistically, we show that dysregulation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARg) in T cells is a causal link between obesity and the increased TH2 immunopathology. We find that PPARg directly controls a cellular metabolic transcriptional program that restrains nuclear gene expression of the chief TH2 effector cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13). Accordingly, thiazolidinediones (TZDs), potent PPARg agonists, robustly protect obese mice from TH2 immunopathology. Collectively, these findings establish PPARg as a molecular link between obesity and TH2 immune homeostasis and identify TZDs as novel therapeutic candidates for TH2 immunopathology.

Publication(s) associated with this dataset:

• Bapat SP, Whitty C, Mowery CT, Liang Y, Yoo A, Jiang Z, Peters MC, Zhang L, Vogel I, Zhou C, Nguyen V, Li Z, Chang C, Zhu WS, Hastie AT, He H, Ren X, Qiu W, Gayer SG, Liu C, Choi EJ, Fassett M, Cohen JN, Sturgill JL, Alexander LE, Suh J, Liddle C, Atkins AR, Yu RT, Downes M, Liu S, Nikolajczyk BS, Lee I, Guttman-Yassky E, Ansel KM, Woodruff PG, Fahy JV, Sheppard D, Gallo RL, Ye CJ, Evans RM, Zheng Y, Marson A. 2022. Obesity alters pathology and treatment response in inflammatory disease. Nature 604:337-342. doi:10.1038/s41586-022-04536-0 PMID:35355021