LL-37 treatment on human peripheral blood mononuclear cells modulates immune response and promotes regulatory T-cells generation

Abstract

LL-37 is a host-defense peptide (HDP) and exerts a broad spectrum of microbicidal activity against bacteria, fungi, and viral pathogens. This peptide also interacts with human cells and influences their behavior, promoting angiogenesis, wound healing, immunomodulation, and affecting apoptosis. Lately, significant advances have been achieved regarding the elucidation of underlying mechanisms related to LL-37 effects over neutrophil and monocytes. However, how T-cells respond to LL-37 stimulation is still largely unknown. Here, we used flow cytometry to evaluate the effects of LL-37 over peripheral blood mononuclear cells (PBMCs) viability, T-cell proliferation, T-cell activation, as well as the generation of regulatory T-cells (Tregs). Those aspects were assessed both in immune homeostatic and inflammatory milieu. Furthermore, we investigated the transcript levels of the inflammatory factors INF-γ, TNF-ɑ, and TGF-β in these conditions. Interestingly, our data revealed that the treatment of PBMCs with LL-37 enhanced the viability of these cells and exerted wide effects over T cell response. Upon activation, LL-37 treated T-cells presented lower proliferation and also increased generation of Tregs. Finally, while non-stimulated cells increased the expression of inflammatory factors when treated with LL-37, activated cells treated with LL-37 presented a decreased production of the same inflammatory mediators. These results are important for the immunotherapy field, and indicate that the use of LL-37 must be carefully evaluated in both homeostatic and inflammatory scenarios, since the microenvironment clearly plays a crucial role in determining how T-cells respond to LL-37.