Skin-Homing Potential of Peripheral Immune Cells From Psoriasis Patients and the Effects of LL-37 on Their Secretion of Chemokines During Psoriasis-Mimicking Stimulation.

Psoriasis is an autoimmune disease of the skin with keratinocyte hyperproliferation and increased skin homing of immune cells. LL-37 is an antimicrobial peptide present at a high level in psoriasis patients. It is thought to participate in the induction of psoriasis and is a potential autoantigen. This study explores the chemokine receptor expression of T cells in psoriasis patients in the context of LL-37 bioavailability in the skin. Thus, chemokines secreted by peripheral blood mononuclear cells (PBMCs), cultured in a psoriasis-mimicking Th1 or Th17 microenvironment, are evaluated in association with LL-37 secretion. The results show that the chemokine receptors CXCR3, CCR4 and CCR6 were expressed at different levels by T cells depending on their expression of the skin-homing and retention markers cutaneous lymphocyte antigen (CLA) and CD103, respectively. A higher proportion of T cells from psoriasis patients expressed CCR6 compared to those from healthy controls, whereas a lower proportion of psoriatic T cells expressed CXCR3. PBMCs stimulated in Th1 and Th17 mimicking microenvironments altered their secretion of many immune biomarkers, further modulated by the addition of LL-37. Principal component analysis revealed that the secretion of chemokines from PBMCs after Th1 stimulation clustered away from the secretion of chemokines after Th17 stimulation. Stimulation of CXCR3expressing CD4T cells revealed less secretory potential than their CXCR3expressing CD4T cells. In summary, LL-37 demonstrated remarkable abilities in modulating the secretion of immune biomarkers by PBMCs, which may cause a change in the microenvironment in the skin in psoriasis.