Inhibitor of the heterochromatin protein 1 (HP1) for modulating th cells
A HP1 inhibitor targets heterochromatin-dependent pathways to modulate Th cell activity, addressing the challenge of integrating inhibitory signals in T cells and enhancing treatment efficacy in autoimmune diseases and cancers by promoting protective responses.
WO2026125263A1PCT designated stage Publication Date: 2026-06-18INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +2
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
- Filing Date
- 2025-12-08
- Publication Date
- 2026-06-18
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Abstract
The present invention relates to a treatment of Th cell-associated disorders. Here, the inventors show that Treg-dependent suppressive signals require HP1α to efficiently repress Th1 and Th17-cell effector genes. Mechanistically, the transcriptional and epigenetic profiling identified HP1γ 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 HP1γ-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 HP1α and HP1γ as new epigenetic players whose expression may be manipulated to strengthen or suppress immune responses, respectively.
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