Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents

Abstract

CD5 and CD6 are closely related signal-transducing class I scavenger receptors mainly expressed on lymphocytes. Both receptors are involved in the modulation of the activation and differentiation cell processes triggered by clonotypic antigen-specific receptors present on T and B cells (TCR and BCR, respectively). To serve such a relevant immunomodulatory function, the extracellular region of CD5 and CD6 interacts with soluble and/or cell-bound endogenous counterreceptors but also microbial-associated molecular patterns (MAMPs). Evidence from genetically-modified mouse models indicates that the absence or blockade of CD5- and CD6-mediated signals results in dysregulated immune responses, which may be deleterious or advantageous in some pathological conditions, such as infection, cancer or autoimmunity. Bench to bedside translation from transgenic data is constrained by ethical concerns which can be overcome by exogenous administration of soluble proteins acting as decoy receptors and leading to transient “functional knockdown”. This review gathers information currently available on the therapeutic efficacy of soluble CD5 and CD6 receptor infusion in different experimental models of disease. The existing proof-of-concept warrants the interest of soluble CD5 and CD6 as safe and efficient immunotherapeutic agents in diverse and relevant pathological conditions.

CD6 deficiency impairs early immune response to bacterial sepsis

“…However, it remains to be tested whether such susceptibility is general and extendable to other infectious agents (e.g., viruses, fungi, or parasites). Indeed, interaction of CD6 with certain viral, fungal, and parasitic structures has been reported ( Velasco-de Andrés et al. , Cells 2020).…”

Molecular Mechanisms Leading from Periodontal Disease to Cancer

“…For CD6, there is still a lack of studies investigating associations with malignancies. Interestingly, the study based on mouse models reported that the absence or blockade of CD5-and CD6-mediated signals resulted in the dysfunction of the immune response, subsequently enhancing cancer progression [175]. Based on the small number of data associating CD5 and CD6 with cancer, we cannot draw a clear conclusion and thus a question remains in mind: are they a potential link between PD and cancer?…”

“…Another example may be Il-17, whose level was increased in ongoing PD [160]. Increased levels of Il-17 promoted the development and epithelial-to-mesenchymal transition in prostate cancer and others [175]. A similar question to the one pertaining to CD5 and CD6 can be raised regarding IL-17.…”

“…For example, two of them were increased CD5 and CD6 levels [162]. CD5 and CD6 molecules play a role in cancer and chronic lymphocytic leukemia [173][174][175]. The CD5 has an inhibitory function in T and B1a cell activation [173].…”

Gene Variation at Immunomodulatory and Cell Adhesion Molecules Loci Impacts Primary Sjögren's Syndrome

“…Both receptors are signal-transducing molecules that modulate intracellular activation and differentiation signals from the antigen-specific receptor complex of T (TCR) and B (BCR) cells to which CD5 and CD6 physically associate (12)(13)(14). In addition, CD5 and CD6 act as pattern recognition receptors (PRRs) by recognizing microbial-associated molecular patterns (MAMPs) from the bacterial, fungal, viral, and parasitic origin (15)(16)(17). Particularly, CD5 has been shown to interact with fungal β-glucans (18), hepatitis C virus (19), and tegumental structures of Echinococcus granulosus (20), while CD6 interacts with lipopolysaccharide, lipoteichoic acid, and peptidoglycan from Gram-negative and -positive bacteria (21), gp120 from human immunodeficiency virus 1 (22), and the tegumental components of E. granulosus (20).…”