CD38: A Significant Regulator of Macrophage Function

Abstract

Cluster of differentiation 38 (CD38) is a cell surface glycoprotein and multifunctional extracellular enzyme. As a NADase, CD38 produces adenosine through the adenosine energy pathway to cause immunosuppression. As a cell surface receptor, CD38 is necessary for immune cell activation and proliferation. The aggregation and polarization of macrophages are affected by the knockout of CD38. Intracellular NAD+ levels are reduced by nuclear receptor liver X receptor-alpha (LXR) agonists in a CD38-dependent manner, thereby reducing the infection of macrophages. Previous studies suggested that CD38 plays an important role in the regulation of macrophage function. Therefore, as a new marker of macrophages, the effect of CD38 on macrophage proliferation, polarization and function; its possible mechanism; the relationship between the expression level of CD38 on macrophage surfaces and disease diagnosis, treatment, etc; and the role of targeting CD38 in macrophage-related diseases are reviewed in this paper to provide a theoretical basis for a comprehensive understanding of the relationship between CD38 and macrophages.

Modulation of tumor‐associated macrophages in colitis‐associated colorectal cancer

“…In dextran sulphate sodium (DSS)-induced acute colitis model of mice, FK866, a NAMPT inhibitor, inhibited the activity of Sirtuin 6 after reducing the level of NAD + in macrophages, inhibited the secretion of pro-inflammatory cytokines by regulating the phosphorylation of NF-κB, and predisposed macrophages to M2 phenotype (Gerner et al, 2018). In addition, CD38 has the ability to catalyze the transformation of NAD + into metabolites such as ADPR, cADPR which up-regulate the expression of T cell activation markers and pro-inflammatory cytokines on the surface of M1 macrophages by regulating cellular calcium ions (W. Li et al, 2022). CD38 knockout reduced intestinal macrophage infiltration and pro-inflammatory cytokine levels, and alleviated DSS induced acute colitis in mice, demonstrating the role of CD38 activity in colitis (Schneider et al, 2015).…”

Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles (EVs) Counteract Inflammaging

“…Interestingly, aged macrophages were hyporesponsive to LPS stimulation, confirming previously published results [ 23 ] and suggesting that metabolic dysregulations play a key role in aged macrophage function. The increased expression of CD38 by the aged macrophages raised our interest, as this marker is necessary not only for immune cell activation [ 48 ], but also for the age-related NAD decline at tissue level. Indeed, CD38 is a multifunctional enzyme that uses NAD as a substrate to generate second messengers and is therefore implicated in the consumption of tissue NAD during the aging process [ 18 ].…”

A nanofiber-hydrogel composite improves tissue repair in a rat model of Crohn’s disease perianal fistulas

“…Activated macrophages are able to differentiate into different subtypes, including M1and M2-like macrophages (34). CD68, CD38, and CD163 have been well used as markers for pan-macrophage, M1-type-like macrophage, and M2-type-like macrophages, respectively (35)(36)(37)(38)(39)(40). The M1-like (CD68 + CD38 + ) cells are associated with a proinflammatory phenotype, while M2-like (CD68 + CD163 + ) cells are associated with a proregenerative phenotype that facilitates tissue regeneration (34).…”