Skin‐Homing Potential of Peripheral Immune Cells From Psoriasis Patients and the Effects of <scp>LL</scp> ‐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^hi. 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 CXCR3^hi expressing CD4⁺ T cells revealed less secretory potential than their CXCR3^neg expressing CD4⁺ T 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.