A novel polypeptide molecule attenuates atopic dermatitis by targeting CCR8-CCL1 axis

Area of Science:

• Immunology
• Dermatology
• Drug Discovery

Background:

• Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with unmet treatment needs.
• Current therapies for AD do not fully address patient requirements.
• Novel therapeutic targets and drug candidates are essential for effective AD management.

Purpose of the Study:

• To discover and develop novel polypeptide inhibitors targeting the CC chemokine receptor 8 (CCR8) pathway for atopic dermatitis treatment.
• To evaluate the efficacy of identified CCR8 polypeptide candidates in preclinical models of AD.

Main Methods:

• Utilized big data and artificial intelligence for polypeptide library screening and drug discovery.
• Conducted in vitro and in vivo studies to assess candidate affinity for human CC chemokine receptor 8 (CCR8).
• Evaluated the therapeutic potential of SP-TG02 in two distinct mouse models of dermatitis.

Main Results:

• Screened two polypeptide candidates with high affinity for human CC chemokine receptor 8 (CCR8).
• Demonstrated that candidates significantly inhibited interstitial dendritic cell (iDC) migration by interfering with the CC chemokine ligand 1 (CCL1)-CCR8 axis.
• SP-TG02 application ameliorated AD-like symptoms, reduced skin damage, mast cell infiltration, and pro-inflammatory cytokine expression in mouse models.

Conclusions:

• SP-TG02, a novel CCR8 polypeptide inhibitor, shows significant therapeutic potential for atopic dermatitis.
• The findings suggest that targeting the CCL1-CCR8 axis is a viable strategy for AD treatment.
• SP-TG02 represents a promising candidate for further development as an atopic dermatitis therapy.