Roles of CD38 in the Immune Response to Infection

Glaría, Estibaliz; Valledor, Annabel F.

doi:10.3390/cells9010228

Cited by 91 publications

(86 citation statements)

References 103 publications

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“…Under physiological conditions, CD38 induced mature Bcell proliferation and immunoglobulin M (IgM) secretion. And in CD38 expressed higher on activated T cells, the CD38 + T cells inhibited CD38 − T-cell proliferation to maintain T-cell homeostasis (Bahri et al, 2012;Glaria and Valledor, 2020). On the contrary, another study have unveiled that T cells expressing high levels of CD38 have an extremely low proliferative ability but an enhanced capacity to produce interleukin 2 (IL-2) and IFN-γ (Sandoval-Montes and Santos-Argumedo, 2005).…”

Section: Discussionmentioning

confidence: 99%

CD38 Predicts Favorable Prognosis by Enhancing Immune Infiltration and Antitumor Immunity in the Epithelial Ovarian Cancer Microenvironment

et al. 2020

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The identification of predictive biomarkers and novel targets to optimize immunotherapy strategies for epithelial ovarian cancer (EOC) is urgently needed. CD38 is a multifunctional glycoprotein that acts as an ectoenzyme and immune receptor. However, the underlying immunological mechanisms and prognostic value of CD38 in EOC remain unclear. CD38 gene expression in EOC was evaluated by using Gene Expression Profiling Interactive Analysis (GEPIA) and TISIDB database. The prognostic value was calculated using GEPIA and Kaplan-Meier plotter. Gene set enrichment analysis was conducted to study the roles of CD38 in the EOC microenvironment. Furthermore, the relationship between CD38 expression level and immune cell infiltration was analyzed by the Tumor Immune Estimation Resource and TISIDB. The GEPIA and TISIDB databases showed that CD38 expression in EOC was higher than that in normal tissue and was highest in the immunoreactive subtype among the four molecular types. A total of 424 cases from GEPIA revealed that high levels of CD38 were associated with longer disease-free survival [hazard ratio (HR) = 0.66, P = 0.00089] and increased overall survival rate (HR = 0.67, P = 0.0016). Kaplan-Meier plotter also confirmed the prognostic value of CD38 in EOC. Data from The Cancer Genome Atlas database demonstrated that gene signatures in many categories, such as immune response and adaptive immune response, were enriched in EOC samples with high CD38 expression. In addition, CD38 was positively correlated with immune cell infiltration, especially infiltration of activated CD8 + T cells, CD4 + T cells, and B cells. CD38 is positively correlated with prognosis and immune cell infiltration in the EOC microenvironment and contributes to the regulation of antitumor immunity. CD38 could be used as a prognostic biomarker and potential immunotherapy target.

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Section: Discussionmentioning

confidence: 99%

CD38 Predicts Favorable Prognosis by Enhancing Immune Infiltration and Antitumor Immunity in the Epithelial Ovarian Cancer Microenvironment

et al. 2020

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“…CD38 expression on monocytes can be induced by pro-inflammatory cytokines ( 53 ). During viral infection down regulation of CD38 has been observed, possibly to reduce virus‐induced hyperinflammation ( 54 ). CD40, a member of the tumor necrosis factor (TNF) receptor family of cell surface proteins, provides strong costimulatory signal to prime T cells.…”

Section: Discussionmentioning

confidence: 99%

Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors

et al. 2020

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Motivation People with HIV on successful antiretroviral therapy show signs of premature aging and are reported to have higher rates of age-associated comorbidities. HIV-associated immune dysfunction and inflammation have been suggested to contribute to this age advancement and increased risk of comorbidities. Method Partial least squares regression (PLSR) was used to explore associations between biological age advancement and immunological changes in the T cell and monocyte compartment in people with HIV (n=40), comparable HIV-negative individuals (n=40) participating in the Comorbidity in Relation to AIDS (COBRA) cohort, and blood donors (n=35). Results We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. Interestingly, a unique monocyte and T cell immune phenotypic profile predictive for age advancement was found within each group. An inflammatory monocyte immune phenotypic profile associated with age advancement in HIV-negative individuals, while the monocyte profile in blood donors and people with HIV was more reflective of loss of function. The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. In people with HIV, age advancement was related to changes in the CD4 + T cell compartment and more reflective of immune recovery after cART treatment. Impact The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. While the monocyte and T cell immune phenotypic profile within the HIV-negative individuals reflected those observed in the combined three groups, a distinct profile related to immune dysfunction, was observed within blood donors and people with HIV. These data suggest that varying exposures to lifestyle and infection-related factors may be associated with specific changes in the innate and adaptive immune system, that all contribute to age advancement.

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“…In contrast, both mature human and mouse T and B cells induce CD38 upon activation. Therefore, this molecule is often used as a cell activation and differentiation marker (7,8,14). Likewise, expression of CD38 in NK cells has been linked to activation, induction of cytotoxic activity, and secretion of IFN-g.…”

Section: Cd38 Distribution In the Immune Systemmentioning

confidence: 99%

“…Since these findings were reported, many studies have sought to understand the extent to which CD38 contributes to the development of inflammatory and autoimmune disease, via modulation of immune responses. So far, it is known that CD38 expression is robustly induced in immune cells after activation and regulates infection-induced inflammatory processes, from cell recruitment to induction of adaptative immune responses (5,14). Nonetheless, the mechanisms utilized by CD38 to mediate each stage of inflammation are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity

et al. 2020

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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.

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Roles of CD38 in the Immune Response to Infection

Cited by 91 publications

References 103 publications

CD38 Predicts Favorable Prognosis by Enhancing Immune Infiltration and Antitumor Immunity in the Epithelial Ovarian Cancer Microenvironment

CD38 Predicts Favorable Prognosis by Enhancing Immune Infiltration and Antitumor Immunity in the Epithelial Ovarian Cancer Microenvironment

Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors

CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity

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