Cell-based high throughput screening identified a novel compound that promotes regulatory T cells and prevents autoimmune colitis

Rui Mao, Haitao Liu, Bing Yi, Sharad Purohit, Michal Kuczma, Piotr Kraj, Jin Xiong She

Research output: Contribution to journalArticle

Abstract

Regulatory T cells (TR) show great promise for treating autoimmune diseases, allergies and preventing transplant rejection; however, their clinical application has been hampered by the lack of efficient ex vivo or in vivo expansion strategies. Here we report screening data on 130,000 low molecular weight (LMW) compounds for their TR promoting potential using a self-developed high-throughput cell-based assay. One of the lead compounds, an isoxazolecarboxamide designated as TRP38, efficiently converts naïve CD4+ T cells to TR cells in vitro and protects mice from autoimmune colitis in vivo. In addition, TRP38 can synergize with other compounds and/or cytokines such as rapamycin and TGFβ for TR conversion, probably via directly inhibiting P70s6 phosphorylation without affecting mTOR expression, underscoring the importance of complementary and coordinated activity of multiple signaling pathways for the increased level of stable TR cell production.

Original languageEnglish (US)
Article number113618
JournalBiochemical Pharmacology
Volume169
DOIs
StatePublished - Nov 2019

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T-cells
Regulatory T-Lymphocytes
Colitis
Screening
Throughput
Lead compounds
Allergies
Transplants
Phosphorylation
Sirolimus
Assays
Molecular weight
Graft Rejection
Cytokines
Autoimmune Diseases
Hypersensitivity
Molecular Weight
T-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Cell-based high throughput screening identified a novel compound that promotes regulatory T cells and prevents autoimmune colitis. / Mao, Rui; Liu, Haitao; Yi, Bing; Purohit, Sharad; Kuczma, Michal; Kraj, Piotr; She, Jin Xiong.

In: Biochemical Pharmacology, Vol. 169, 113618, 11.2019.

Research output: Contribution to journalArticle

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