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Review
. 2020 Nov 30:11:597959.
doi: 10.3389/fimmu.2020.597959. eCollection 2020.

CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity

Zayda L Piedra-Quintero  1 , Zachary Wilson  1   2 , Porfirio Nava  3 , Mireia Guerau-de-Arellano  1   4   5   6
Affiliations
Review

CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity

Zayda L Piedra-Quintero et al. Front Immunol. .

Abstract

CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity, or as a receptor with adhesive functions. CD38 can be found expressed either on the cell surface, where it may face the extracellular milieu or the cytosol, or in intracellular compartments, such as endoplasmic reticulum, nuclear membrane, and mitochondria. The main expression of CD38 is observed in hematopoietic cells, with some cell-type specific differences between mouse and human. The role of CD38 in immune cells ranges from modulating cell differentiation to effector functions during inflammation, where CD38 may regulate cell recruitment, cytokine release, and NAD availability. In line with a role in inflammation, CD38 appears to also play a critical role in inflammatory processes during autoimmunity, although whether CD38 has pathogenic or regulatory effects varies depending on the disease, immune cell, or animal model analyzed. Given the complexity of the physiology of CD38 it has been difficult to completely understand the biology of this molecule during autoimmune inflammation. In this review, we analyze current knowledge and controversies regarding the role of CD38 during inflammation and autoimmunity and novel molecular tools that may clarify current gaps in the field.

Keywords: ADP-ribosyl cyclase; CD38; NADase; autoimmunity; cADPR hydrolase; inflammation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Expression of CD38 in human and mouse tissue. (A) CD38 is ubiquitously expressed in the human and mouse body. (B) Schematic representation of CD38 expression on immune cells. The differences in CD38 expression between human and mouse is highlighted [adapted from (29, 30)]. This figure was created using Biorender (https://biorender.com). B, B cell; PC, Plasma cell; NK, Natural Killer cell; DC, Dendritic Cell; T, T cell; Mo, Monocyte; PMN, Molymorphonuclear cell; HSC, Hematopoietic Stem Cell.
Figure 2
Figure 2
Role of CD38 during inflammation. The figure displays a schematic representation of an inflammatory process and the events impacted by CD38. During inflammation, CD38 can modulate cell recruitment, cytokines and chemokines release, cell activation, phagocytosis, and antigen presentation. CD38 expressing cells consume NAD+ to produce cADPR an event that leads to inflammation. This figure was created using Biorender (https://biorender.com).
Figure 3
Figure 3
Molecular tools to analyze CD38’s functions.
See this image and copyright information in PMC

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