Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Burns, Marie; Ostendorf, Lennard; Biesen, Robert; Grützkau, Andreas; Hiepe, Falk; Mei, Henrik E.

doi:10.3390/ijms22052424

Cited by 26 publications

(28 citation statements)

References 60 publications

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“…In fact, a trial in patients with SLE who were resistant to anti-TNFα therapy found that targeting CD38 with daratumumab, which depletes CD38 expressing cells, ameliorates disease 58 . Our data show that multiple circulating and cutaneous cell types in patients with HS upregulate CD38, which is involved in multiple mechanisms that enhance inflammation 27,28,30,34,35,59 . Our IHC and bioinformatic analysis also found a robust increase of CD38 in lesional, but not perilesional HS skin.…”

Section: Discussionmentioning

confidence: 74%

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa

Dimitrion

Hamzavi

Yin

et al. 2023

Preprint

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Background: Hidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved. Objective: Identify features of peripheral and cutaneous immune dysregulation. Methods: Here, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS. Results: Blood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin. Conclusion: Circulating and cutaneous immune cells in patients with HS harbor dysregulated expression of CD38.

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Section: Discussionmentioning

confidence: 74%

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa

Dimitrion

Hamzavi

Yin

et al. 2023

Preprint

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“…In rheumatoid arthritis (RA), the inhibition of CD38 activation by anti-CD38 monoclonal antibody has been effective to reduce RA symptoms and disease progression. In systemic lupus erythematosus (SLE) patients, the upregulation of CD38 expression in marginal zone-like IgD + CD27 + B cells has been reported ( 72 ), and the depletion of CD38 in pristane-induced lupus mouse model significantly improve the symptom ( 73 ). Thus, CD38 upregulation in B cells seems to be related to inflammatory status.…”

Section: Discussionmentioning

confidence: 99%

Radiation therapy induces immunosenescence mediated by p90RSK

Imanishi

Cheng

Kotla

et al. 2022

Front. Cardiovasc. Med.

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Radiation therapy (RT) to the chest increases the patients’ risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. We isolated peripheral blood mononuclear cells (PBMCs) before and 3 months after RT from 16 thoracic cancer patients. We characterized human immune cell lineages and markers of senescence, DNA damage response (DDR), efferocytosis, and determinants of clonal hematopoiesis of indeterminant potential (CHIP), using mass cytometry (CyTOF). We found that the frequency of the B cell subtype was decreased after RT. Unsupervised clustering of the CyTOF data identified 138 functional subsets of PBMCs. Compared with baseline, RT increased TBX21 (T-bet) expression in the largest B cell subset of Ki67–/DNMT3a+naïve B cells, and T-bet expression was correlated with phosphorylation of p90RSK expression. CD38 expression was also increased in naïve B cells (CD27–) and CD8+ effector memory CD45RA T cells (TEMRA). In vitro, we found the critical role of p90RSK activation in upregulating (1) CD38+/T-bet+ memory and naïve B, and myeloid cells, (2) senescence-associated β-gal staining, and (3) mitochondrial reactive oxygen species (ROS) after ionizing radiation (IR). These data suggest the crucial role of p90RSK activation in immunosenescence. The critical role of p90RSK activation in immune cells and T-bet induction in upregulating atherosclerosis formation has been reported. Furthermore, T-bet directly binds to the CD38 promoter region and upregulates CD38 expression. Since both T-bet and CD38 play a significant role in the process of immunosenescence, our data provide a cellular and molecular mechanism that links RT-induced p90RSK activation and the immunosenescence with T-bet and CD38 induction observed in thoracic cancer patients treated by RT and suggests that targeting the p90RSK/T-bet/CD38 pathway could play a role in preventing the radiation-associated CVD and improving cancer prognosis by inhibiting immunosenescence.

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“…The Change of CD38inchondrocytesis Associated with OA Development CD38 has been proven to be correlated with autoimmune diseases like Systemic Lupus Erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) [23][24][25] . However, whether or not CD38 is involved in the progression of OA is still unclear.…”

Section: Discussionmentioning

confidence: 99%

CD38 Drives Progress of Osteoarthritis by Affecting Cartilage Homeostasis

Ying

Wang

et al. 2022

Orthopaedic Surgery

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Objective To observe expression of CD38, a key modulator of nicotinamide dinucleotide (NAD+) metabolism in mice with knee osteoarthritis, and protective effect of CD38 inhibition during the osteoarthritis (OA) development. Method The destabilization of the medial meniscus (DMM) model was performed in mice to mimic the process of OA. Immunofluorescence of CD38 was performed to evaluate its response during the OA process. Limb bud‐derived mesenchymal cells were isolated for micromass culture. 100 nM or 1 μM CD38 inhibitor (78c) treatment for 14 days and CD38 sgRNA infection were then used to explore the effects of chondrogenic differentiation via Alcian blue staining. The expressions of chondrogenic markers were detected using RT‐PCR and Western blot. To explore the protective effect of CD38 inhibitor on cartilage degradation during OA in vivo, a CD38 inhibitor was injected into the knee joint after DMM operations. Micro‐CT analysis and Safranin O‐fast green staining were used to evaluate subchondral bone micro‐architecture changes and cartilage degeneration. Results Compared to the control group, the CD38 expression in superficial cartilage was obviously increased in DMM group (P < 0.05). During the normal chondrogenic differentiation, the extracellular matrix formed and expression of Sox9, Col2, aggrecan increased apparently while CD38 expression decreased, which could be reversed with ablation of CD38 in limb bud‐derived mesenchymal cells. Consistent with findings in vitro, CD38 blockage via CD38 inhibitor injection protected against osteosclerosis in medial subchondral bone and cartilage degeneration in DMM‐induced experimental mice. Compared to the Sham group, DMM mice showed significantly increased values of BV and BV/TV in subchondral bone (P < 0.05) and Mankin score, which could be rescued by 78c treatment (P < 0.05). Also the CD38 inhibitor contributed to homeostasis of anabolism and catabolism by upregulating Sox9, Col2, aggrecan and downregulating Runx2, Col10 and Mmp13. Conclusion This study primarily implicates CD38 as an important regulator of chondrogenic differentiation. Inhibition of CD38 demonstrated protection against cartilage degeneration, which suggests that CD38 could be a potential therapeutic target for OA.

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Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Cited by 26 publications

References 60 publications

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa

Radiation therapy induces immunosenescence mediated by p90RSK

CD38 Drives Progress of Osteoarthritis by Affecting Cartilage Homeostasis

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