Sustaining the T-cell activity in xenografted psoriasis skin

Area of Science:

• Immunology
• Dermatology
• Preclinical models

Background:

• Psoriasis xenografts on immunodeficient mice are crucial for drug candidate testing.
• A key limitation is the absence of human T-cell activity in these grafts.

Purpose of the Study:

• To evaluate human IL-2 NOG mice as a model for psoriasis xenografts with enhanced human T-cell activity.
• To assess the potential of this model for future drug efficacy studies.

Main Methods:

• Lesional skin from psoriasis patients was xenografted onto human IL-2 NOG mice, C.B-17 scid, and NOG mice.
• Human CD3+ cell infiltration, cytokine levels, and drug efficacy (ustekinumab) were analyzed.

Main Results:

• Human IL-2 NOG mice exhibited significantly higher numbers of human CD3+ cells in grafts, lymph nodes, and blood compared to control mice.
• Elevated levels of disease-relevant human cytokines were detected in graft lysates and serum.
• The epidermis was absent in grafts, and ustekinumab showed no efficacy.

Conclusions:

• Human IL-2 NOG mice support enhanced human T-cell activity in psoriasis xenografts.
• Despite improved T-cell presence, the model needs further refinement to fully replicate psoriasis pathology and assess drug efficacy.