CD38: A Significant Regulator of Macrophage Function.

Wentao Li,Yanling Li,Qianjin Liao,Zhifang Chen,Xi Jin,Yanhong Zhou,Honghua Peng

doi:10.3389/fonc.2022.775649

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.

Highlights

Cluster of differentiation 38 (CD38) is a cell surface glycoprotein and multifunctional extracellular enzyme which is primarily a NAD+ glycohydrolase and adenosine diphosphate-ribose (ADPR) cyclase [1]
it ubiquitously expressed in immune cells
most of the NAD+ catalyzed by CD38 is converted to adenosine diphosphate-ribose

Summary

INTRODUCTION

Cluster of differentiation 38 (CD38) is a cell surface glycoprotein and multifunctional extracellular enzyme which is primarily a NAD+ glycohydrolase and ADPR cyclase [1]. Pro-inflammatory M1-like macrophages, rather than naive or M2 macrophages, were accumulated in metabolic tissues, including the visceral white adipose tissue and liver, during aging and the acute inflammatory response Among 54 patients infected with HIV with virus inhibition, the level of CD14CD38 (% CD14) increased significantly in 20 patients with significantly reduced memory ability [34] This suggested that the expression level of CD38 on the surface of macrophages might be related to the diagnosis of disease. Similar results were obtained by targeting CD38 pharmacologically by administering the CD38 inhibitor, k-rhein [2]

The mechanism comprises the activation of immune cells

SUMMARY AND PROSPECTS