Non-canonical NF-kB pathway crosstalk with HIF-1a and its effects on Tregs activity and differentiation

• Grant number: 23/06622-5
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 01, 2023
• End date: November 25, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Natalia Notarberardino Bos
• Supervisor: Ari Waisman
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Johannes Gutenberg University Mainz (JGU), Germany
• Associated to the scholarship: 22/13074-1 - Regulation of the Th17/Treg axis by HIF-1a in experimental type 1 diabetes susceptibility, BP.IC

Abstract

HIF-1 is a transcription factor that enables cells to adapt to low oxygen levels through glycolysis. This metabolic plasticity is vital for immune cell survival and differentiation, regulated by HIF-1alpha. HIF-1alpha also influences the balance between Treg and Th17 cells, suggesting metabolic pathways as potential targets for immune-mediated diseases. In addition, NFkB is a critical transcription factor regulating immune responses, inflammation, and cancer. It responds to various stimuli and has two activation pathways. The canonical pathway involves NEMO, IKKalpha, and IKKbeta, leading to NFkB dimer release for gene regulation. The non-canonical pathway relies on NIK and IKKalpha for protein stabilization and phosphorylation. NFkB plays a crucial role in Treg development and function, and non-canonical signaling influences Tregs. Understanding the interplay between NFkB and HIF-1a in immune cells, particularly in regulatory T cells, is essential for therapeutic advancements in autoimmune diseases. The crosstalk between NFkB and HIF-1a occurs in various immune cells, impacting immune regulation and T cell development. Further research is needed to unravel the non-canonical NFkB activation and its association with HIF-1a in regulatory T cells, providing insights for immune mechanisms and therapeutic strategies in autoimmune diseases. (AU)