لخّصلي

The earliest studies of the non-microbicidal properties of CHDP focused on their effects on immune cells, particularly their ability to recruit leukocytes. Over the past two decades, research has uncovered a wide range of immune-related functions for CHDP, with these functions dependent on environmental stimuli, cell and tissue type, interactions with cellular receptors, and peptide concentration. The molecular mechanisms underlying CHDP's selective modulation of immune responses are intricate and involve intracellular uptake, potentially mediated by GPCRs, interactions with proteins like GAPDH and p62, alterations in signaling pathways (NF-κB, p38 and JNK MAPK, MKP1, and PI3K), and engagement of transcription factors. These processes are influenced by peptide concentration, response kinetics, and environmental stimuli. The diverse immunomodulatory functions of CHDP raise questions about their primary biological role. This review summarizes the activities of CHDP on immunity and inflammation, focusing on cathelicidins and defensins. Comprehending the mechanisms behind CHDP's ability to modulate immunity for infection protection, inflammation resolution, and immune homeostasis is crucial for developing novel therapeutic approaches based on CHDP-derived peptides.

Immunomodulatory actions of CHDP
The earliest studies of the non-microbicidal properties of CHDP were on their effects on immune cells, related primarily to the ability of these peptides to recruit leuko- cytes125–127. Following this, research on immunity-related functions of CHDP increased exponentially over the next two decades, defining a diverse range of functions. Immunity-related functions of CHDP seem to be depen- dent on the environmental stimuli, cell and tissue type, interaction with different cellular receptors and the concentration of the peptides. Studies to date indicate that the molecular mechanism underpinning the ability of CHDP to selectively modulate immune responses is highly complex, involving intracellular uptake of the peptides, which may or may not be mediated by membrane-associated G protein-coupled receptors (GPCRs), interaction with several intracellular interact- ing protein partners or receptors (for example, GAPDH and p62), alteration of several signalling pathways (nuclear factor-κB (NF-κB), p38 and JNK mitogen- activated protein kinase (MAPK), MKP1 and phospho- inositide 3-kinase (PI3K)) and engagement of different transcription factors, all of which seem to be dependent
on factors such as the peptide concentration, the kinet- ics of response and the environmental stimuli (reviewed in refs12,15,128,129). The pleiotropic immunomodulatory functions of CHDP raise questions regarding the primary biological role of these peptides. In the following sub- sections, we summarize the activities of CHDP on modu- lation of immunity and inflammation (fig. 3), focusing primarily on cathelicidins and defensins. Understanding the mechanisms that underpin the ability of CHDP to modulate immunity to protect against infection, resolve inflammation and contribute to immune homeostasis is critical to the development of novel therapeutic approaches based on CHDP-derived peptides.