Role of Chemokine and Chemokine Receptor in Psoriasis

Chemokines belongs to a large group of small chemotactic proteins (8-11 kilodaltons in size).
Upon engagement of chemokine, chemokine receptor can activate downstream intracellular
signaling pathways and results in diverse cellular processing such as cytoskeleton
reorganization and cell locomotion. Chemokines are chemoattractant factors and can stimulate
directional migration of all classes of leukocytes such as T cells. Epidermal keratinocytes
in the skin are able to express multiple chemokines that can attract certain leukocytes, such
as T cells or dendritic cells (DCs), to migrate to the epidermis. Psoriasis is a type of skin
inflammatory diseases that results in misregulated immune system including immune cell
infiltration. Keratinocyte secreted chemokine and chemokine receptor on leukocytes have been
known to involve in the pathogenesis of psoriasis. However, it is not very clear how
chemokines are regulated in keratinocytes and the binding of chemokine to receptor on
leukocytes controls the pathogenesis of psoriasis. To better understand the immune regulation
of chemokine and chemokine receptor in the molecular mechanism and pathogenesis of psoriasis,
the investigators plan to establish human psoriasis skin xenograft mouse model that involves
graft of human skin onto immune deficient mice. The human skin, including lesional and
non-lesional skins, has been proven to be acceptable to the SCID mice and the phenotype can
maintain for a number of months. The advantage of the xenograft model is to that it can
preserve the full complexity of human diseases and thus resembles the pathogenesis of human
diseases. This model has also been shown with constant efficacy of anti-psoriasis drug in
comparison with clinical practice. Thus, this mouse model has great value to help the
investigators understand how chemokine and immune cells are regulated in psoriasis. Of
particular note is that this model can be used to test therapeutic drug before introduce them
into clinical trial.

Inclusion Criteria:

- Subjects 18 years of age or greater

- Subjects need to fulfill the diagnostic evidence of psoriasis with or without
psoriatic arthritis

- Subject may take the following medicines: NSAID, hydroxychloroquine, sulfasalazine,
prednisone (<10 mg/day), Methotrexate (10 mg/week)

- Subject needs to stop topical skin preparations other than emollients in one small
plaque of psoriasis for 3-4 wks from where the shave biopsy will be taken

- Willing and able to provide informed consent in English

Exclusion Criteria:

- Subjects less than 18 years old

- no clinical evidence of psoriatic skin

- Subjects with contraindications for biopsy, and patients receiving anticoagulants

- Subjects with active hepatitis B or Hepatitis C infection

- Subjects with concomitant inflammatory diseases such as inflammatory bowel disease,
gout

- Subjects who are taking the following systemic biological therapies for psoriasis:
cyclosporine, methotrexate, prednisone, acitretin, sulfasalazine, certolizumab,
etanercept, adalimumab, infliximab, golimumab, secukinumab, ustekinumab, and
apremilast. Other systemic medications may exclude the subject from the study.