Back to resultsINHIBITOR OF THE HETEROCHROMATIN PROTEIN 1 (HP1) FOR MODULATING TH CELLS
The present invention relates to a treatment of Th cell-associated disorders. Here, the
inventors The inventors show that Treg-dependent suppressive signals require HP1 to
efficiently repress Th1 and Th17-cell effector genes. Mechanistically, the transcriptional and
epigenetic profiling identified HP1/ as a negative regulator of a gene network functionally
associated with T-cell anergy and exhaustion, including those encoding the transcription factor
TOX and the inhibitory receptors PD-1, TIM-3 and LAG-3. In response to T cell receptor
engagement, the expression of these immune checkpoints is upregulated in HP1-deficient
cells, thus enhancing the ability of Tregs to suppress Th cells. Therefore, the inventors
demonstrate that heterochromatin-dependent epigenetic pathways critically regulate Th cell susceptibility to Treg-mediated suppression, and they identify HP1 and HP1 as new
epigenetic players whose expression may be manipulated to strengthen or suppress immune
responses, respectively.
inventors The inventors show that Treg-dependent suppressive signals require HP1 to
efficiently repress Th1 and Th17-cell effector genes. Mechanistically, the transcriptional and
epigenetic profiling identified HP1/ as a negative regulator of a gene network functionally
associated with T-cell anergy and exhaustion, including those encoding the transcription factor
TOX and the inhibitory receptors PD-1, TIM-3 and LAG-3. In response to T cell receptor
engagement, the expression of these immune checkpoints is upregulated in HP1-deficient
cells, thus enhancing the ability of Tregs to suppress Th cells. Therefore, the inventors
demonstrate that heterochromatin-dependent epigenetic pathways critically regulate Th cell susceptibility to Treg-mediated suppression, and they identify HP1 and HP1 as new
epigenetic players whose expression may be manipulated to strengthen or suppress immune
responses, respectively.
Patent Application number:
European Procedure (Patents) (EPA) - 09 Déc. 2024 - 24 307 053.9
Inventors:
NOGUEROL Julie; LAVIOLETTE Karl; ZAHM Margot
Publications:
Noguerol J, Laviolette K, Zahm M, Chaubet A, Sahal A, Détraves C, Torres R, Demont C, Adoue V, Joffre C, Cammas F, van Meerwijk JP, Joffre OP. Heterochromatic gene silencing controls CD4+ T cell susceptibility to regulatory T cell-mediated suppression in a murine allograft model. Nat Commun. 2025 Jan 10;16(1):566. doi: 10.1038/s41467-025-55848-4. PMID: 39794349; PMCID: PMC11723947.
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