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.
Highlights
Scavenger Receptors (SRs) comprise a structurally diverse superfamily of proteins involved in a wide range of biological functions through the recognition of a variety of endogenous and exogenous structures [1,2]
It was observed that (i) production of echinoccocal infection-protective pro-inflammatory cytokines (i.e., TNF-α and IL-6) following PSEx exposure of mouse wild-type (WT) peritoneal cells was increased in the presence of recombinant soluble human CD5 (rshCD5), and (ii) peritoneal cells from cd5−/− mice challenged with PSEx produced lower amounts of IL-6 compared with WT
In order to assess the in vivo use of soluble form of CD5 (sCD5) as a decoy receptor in cancer therapy, a transgenic mouse line that constitutively expresses the soluble portion of human CD5 under control of the non-tissue specific SV40 promoter and immunoglobulin μ heavy chain enhancer (Eμ) was developed [69]
Summary
Scavenger Receptors (SRs) comprise a structurally diverse superfamily of proteins involved in a wide range of biological functions through the recognition of a variety of endogenous and exogenous structures [1,2]. SRs are mainly expressed by cells from epithelial barriers and the innate immune system, but T and B lymphocytes, the prototypical cell type of the adaptive immune system, are equipped with some representatives of the SR superfamily This is the case of CD5 and CD6 receptors, two members of the class I type SRs, defined by the presence of several scavenger receptor cysteine-rich (SRCR) domain repeats [3]. Cells 2020, 9, 2589 of human and mouse chromosomes 11 and 9, respectively [1] Both are integral trans-membrane glycoproteins, characterized by three extracellular SRCR domains and a cytoplasmic tail adapted for intracellular signal transduction, in spite of lacking intrinsic catalytic activity [4]. CMV, cytomegalovirus; HIV, human immunodeficiency virus; Created with BioRender.com
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