Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.
Lin DuBo Man HoLinbin ZhouYolanda Wong Ying YipJing Na HeYingying WeiClement Chee Yung ThamSun On ChanAndrew V SchallyChi Pui PangJian LiWai-Kit ChuPublished in: Nature communications (2023)
Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation. We find that GHRH-R is not expressed in naïve CD4 + T cells, while its expression is induced throughout Th17 cell differentiation in vitro. Mechanistically, GHRH-R activates the JAK-STAT3 pathway, increases the phosphorylation of STAT3, enhances both non-pathogenic and pathogenic Th17 cell differentiation and promotes the gene expression signatures of pathogenic Th17 cells. Enhancing this signaling by GHRH agonist promotes, while inhibiting this signaling by GHRH antagonist or GHRH-R deficiency reduces, Th17 cell differentiation in vitro and Th17 cell-mediated ocular and neural inflammation in vivo. Thus, GHRH-R signaling functions as a critical factor that regulates Th17 cell differentiation and Th17 cell-mediated autoimmune ocular and neural inflammation.
Keyphrases
- growth hormone
- oxidative stress
- gene expression
- single cell
- cell therapy
- multiple sclerosis
- induced apoptosis
- stem cells
- signaling pathway
- dna methylation
- diabetic rats
- cell proliferation
- binding protein
- endothelial cells
- pseudomonas aeruginosa
- transcription factor
- drug induced
- optic nerve
- long non coding rna
- high glucose
- protein kinase
- escherichia coli
- optical coherence tomography
- bone marrow