DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis

Cai, Ming; Zhou, Tong; Wang, Xuan; Shang, Minghua; Zhang, Yueyue; Luo, Man; Che, Xu; Wang, Yuan

doi:10.1111/cei.12723

Cited by 21 publications

(12 citation statements)

References 24 publications

(36 reference statements)

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“…Several genes decreased in aged female mice compared to young female mice, including those involved in xenobiotic metabolism (Inmt, Hpd, Ces1e) and Cluster of Differentiation 209 (Cd209a) (aka. Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin, DC-SIGN) ( Figure 2B ), which co-expresses with nephrin in podocytes [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

Sex differences in transcriptomic profiles in aged kidney cells of renin lineage

Wang

Eng

Pippin

et al. 2018

Aging

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Renin expressing cells in the kidney’s juxta-glomeruluar compartment likely also serve as progenitors for adult glomerular cells in disease. Although these cells of renin lineage (CoRL) decrease in number with advancing kidney age, accompanied by less responsiveness to typical stimuli such as ACE-inhibition, mechanisms and the impact of sex as a biological variable with age are not known. Accordingly, labeled CoRL were sorted from individual young (2m) and aged (27m) male and female Ren1cCre|ZsGreen reporter mice, and their transcriptomic profiles analyzed by RNA seq. When both aged female and male mice were combined, there were 48 differentially expressed genes (DEG) compared to young mice. However, when compared to their young sex-matched mice, aged female and male mice had 159 and 503 DEGs respectively. In addition to marked differences in individual genes between aged female and male mice, gene ontology analysis showed major pathway differences by sex. The majority of DEGs in one sex did not significantly change or changed in the opposite direction in the other sex. These results show that in CoRL of advanced age, individual genes and gene ontologies change, but differ between female and male mice, highlighting sex related differences the aging process.

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Section: Resultsmentioning

confidence: 99%

Sex differences in transcriptomic profiles in aged kidney cells of renin lineage

Wang

Eng

Pippin

et al. 2018

Aging

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“…One study evaluated the level of CD209 in psoriasis vulgaris lesions, and reported that CD209 was higher in psoriasis lesions compared with normal tissues [ 16 ]. A recent study showed the expression of CD209 on podocytes and its possible role in immune and inflammatory responses in lupus nephritis [ 42 ]. In this study, CD209 circulating granulocytes correlated with systemic scores, ESR, and levels of CRP, ferritin, LDH, IL-23, and IL-18.…”

Section: Discussionmentioning

confidence: 99%

Highly Expression of CD11b and CD32 on Peripheral Blood Mononuclear Cells from Patients with Adult-Onset Still’s Disease

Kim

Choi

Suh

et al. 2017

IJMS

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Background: We investigated the potential role of several pattern-recognition receptors (PRRs; CD11b, CD11c, CD32, CD206, CD209, and dectin-1) in adult-onset Still’s disease (AOSD). Methods: The study included 13 untreated AOSD patients, 19 rheumatoid arthritis (RA) patients (as a disease control), and 19 healthy controls (HCs). The PRRs were quantified in peripheral blood using flow cytometry. The serum levels of interleukin-17 (IL-17), IL-18, and IL-23 were measured by enzyme-linked immunosorbent assay. Results: Significantly higher mean frequencies of cells presenting CD11b and CD32 from whole blood were observed in patients with AOSD than in patients with RA or HC. The levels of IL-17, IL-18, and IL-23 were elevated in AOSD patients compared to HCs. CD11b frequencies from whole cells correlated with systemic scores, lactate dehydrogenase (LDH) levels, aspartate transaminase levels, interleukin-23 (IL-23) levels, and IL-18. Frequencies of CD209 from granulocytes were significantly correlated with systemic scores, and the erythrocyte sedimentation rate and levels of C-reactive protein, ferritin, LDH, IL-23, and interleukin-18 (IL-18). Conclusions: Elevated frequencies of circulating CD11b-positive cells and positive correlations with disease activity markers suggest that circulating CD11b-positive cells contribute to the pathogenesis of AOSD.

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“…10 DC-SIGN is co-expressed with nephrin on podocytes in the renal tissues of patients with lupus nephritis. 11 There is a significant correlation between DC-SIGN expression on the tubulointerstitium and the severity of tubulointerstitial lesions. 12 Thus it appears that the expression of DC-SIGN on non-immune cells may modulate the outcomes of the disease.…”

Section: Introductionmentioning

confidence: 99%

Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis

Chen

Lin

et al. 2018

Cell Mol Immunol

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We generated a human dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) transgenic mouse in which renal tubular epithelial cells expressed DC-SIGN. The transgenic mice were infected with Candida albicans intravenously to study how DC-SIGN expression affected the pathogenesis of systemic candidiasis. We discovered that, while C. albicans infection induced renal fibrosis in both transgenic and littermate control mice, the transgenic mice had significantly lower levels of Acta2, Col1a2, Col3a1, and Col4a1 mRNA transcripts compared to the controls. KIM-1, an emerging biomarker for kidney injury, along with Tnf, Il6, and Tgfb1 transcripts, were lower in infected transgenic mice, and yet, the levels of Il10 remained comparable to the controls. While renal CD45 infiltrating cells were the source of Tnf, Il6, and Il10, LTL renal proximal tubular epithelial cells were TGF-β1 producers in both infected transgenic and littermate controls. DC-SIGN-expressing tubular epithelial cells produced less TGF-β1 in response to C. albicans infection. In vivo experiments demonstrated that renal proximal tubular epithelial cell production of TGF-β1 was key to C. albicans-induced renal fibrosis and injury. Infection of transgenic mice induced a marked increase of phosphorylated Raf-1 and p38 in the kidney. However, ERK1/2 and JNK phosphorylation was more pronounced in the infected-littermate controls. Interestingly, treating the infected transgenic mice with a Raf-1 inhibitor increased the levels of the Tgfb1, Kim1, and Acta2 transcripts. These results indicate that DC-SIGN signaling, through activation of Raf-1 and p38 and suppression of JNK and ERK1/2 phosphorylation, reduces TGF-β1 production and C. albicans-induced renal fibrosis. Our study reveals for the first time the effect of DC-SIGN expression on C. albicans-induced renal fibrosis.

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DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis

Cited by 21 publications

References 24 publications

Sex differences in transcriptomic profiles in aged kidney cells of renin lineage

Sex differences in transcriptomic profiles in aged kidney cells of renin lineage

Highly Expression of CD11b and CD32 on Peripheral Blood Mononuclear Cells from Patients with Adult-Onset Still’s Disease

Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis

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