Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

Shenoy, Satyanarayana N.; Chaurasia, Smriti; Edavalath, Sukesh; Zanwar, Abhishek; Agrawal, Vinita; Aggarwal, Amita; Misra, Ramnath

doi:10.1111/1756-185x.13272

Cited by 10 publications

(3 citation statements)

References 33 publications

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“…Our results are in accordance with previous studies which demonstrated up-regulation of the Th17-axis in SLE compared to control, but failed to find an association between Th17 responses and disease activity [9][10][11]. Moreover, in the available literature there was usually no association between increased levels of IL-17A or a higher fraction of Th17 cells and the presence of nephritis in SLE patients [8][9][10][11]14] with only few studies demonstrating clear expansion of Th17 in more severe proliferative LN [26,27]. Inconsistencies between various studies may be attributed to different strategies in detection of the Th17 subset, e.g.…”

Section: Discussionsupporting

confidence: 91%

Facilitated expansion of Th17 cells in lupus nephritis patients

Jakieła

Kosałka

Plutecka

et al. 2018

Clinical and Experimental Immunology

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The objective of this study was to investigate the mechanisms of T helper type 17 (Th17) expansion in lupus nephritis (LN) patients, and to determine whether or not it is associated with impaired function of regulatory T cells (T ). Major effector subsets of peripheral blood CD4 T cells were assessed by flow cytometry in 33 LN patients with different activity of the disease and 19 healthy controls. The percentage of circulating Th17 cells was increased in LN (median = 1·2% of CD4 compared to 0·6% in the control group, P < 0·01), while T cells remained unchanged (12·3 versus 12·1% in controls), resulting in a significantly lower T /Th17 ratio. Th17 expansion in the patient group was not related to LN activity, renal histology or blood and urine inflammatory biomarkers, but has been associated with a higher cumulative dose of cyclophosphamide. T cells in LN displayed mainly effector memory phenotype and expressed higher levels of transforming growth factor (TGF)-β; however, their suppressant activity in lymphocyte proliferation assay was diminished compared to controls (~fourfold, P < 0·05). Co-culture of T and conventional CD4 T cells resulted in marked suppression of the Th1 subset in both of the groups studied, but also in a potent expansion of Th17 cells, which in LN was twofold higher, as in controls (P < 0·05). In conclusion, our results demonstrate that Th17 expansion in LN is not increased during disease exacerbation, but is related to chronic immunosuppressive therapy. This immune signature is probably linked to the abnormal function of T cells, which were less suppressive in LN patients and even facilitated differentiation of Th17 cells.

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Section: Discussionsupporting

confidence: 91%

Facilitated expansion of Th17 cells in lupus nephritis patients

Jakieła

Kosałka

Plutecka

et al. 2018

Clinical and Experimental Immunology

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“…2A, 2B), these effects were inhibited in the Tris DBA + ASLN mice. In contrast, Treg cells have been shown to play a protective role in SLE (31,38) and LN (39,40). We determined the population of Foxp3 + CD25 + CD4 + Treg cells, and the results showed that a significantly increased percentage of Foxp3 + CD25 + CD4 + Treg cells was observed at week 5 in the Tris DBA + ASLN mice compared with the Vehicle + ASLN mice (Fig.…”

Section: Tris Dba Modulated T Cell Function In Asln Micementioning

confidence: 91%

Tris DBA Ameliorates Accelerated and Severe Lupus Nephritis in Mice by Activating Regulatory T Cells and Autophagy and Inhibiting the NLRP3 Inflammasome

Hua

Chu

et al. 2020

The Journal of Immunology

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Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small-molecule palladium complex, has been shown to inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukemia, and multiple myeloma. In the current study, we examined the therapeutic effects of Tris DBA on glomerular cell proliferation, renal inflammation, and immune cells. Treatment of accelerated and severe lupus nephritis (ASLN) mice with Tris DBA resulted in improved renal function, albuminuria, and pathology, including measurements of glomerular cell proliferation, cellular crescents, neutrophils, fibrinoid necrosis, and tubulointerstitial inflammation in the kidneys as well as scoring for glomerulonephritis activity. The treated ASLN mice also showed significantly decreased glomerular IgG, IgM, and C3 deposits. Furthermore, the compound was able to 1) inhibit bone marrow-derived dendritic cell-mediated T cell functions and reduce serum anti-dsDNA autoantibody levels; 2) differentially regulate autophagy and both the priming and activation signals of the NLRP3 inflammasome; and 3) suppress the phosphorylation of JNK, ERK, and p38 MAPK signaling pathways. Tris DBA improved ASLN in mice through immunoregulation by blunting the MAPK (ERK, JNK)-mediated priming signal of the NLRP3 inflammasome and by regulating the autophagy/NLRP3 inflammasome axis. These results suggest that the pure compound may be a drug candidate for treating the accelerated and deteriorated type of lupus nephritis.

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“…1 Furthermore, circulating Th17 cells were significantly raised in patients with active proliferative lupus nephritis, but significantly reduced in responder patients following therapy. 2 The role of Th17 cells in the pathogenesis of SLE provides a potential and promising approach for treatment of SLE.…”

Section: Introductionmentioning

confidence: 99%

Leptin facilitates the differentiation of Th17 cells from MRL/Mp-Fas lpr lupus mice by activating NLRP3 inflammasome

Zhang

et al. 2019

Innate Immun

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Both NLRP3 inflammasome and Th17 cells play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here we tried to investigate whether leptin promotes the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome. Th17 cells induced from MRL/Mp-Fas lpr mice splenocytes under Th17 polarizing condition were treated with leptin at scalar doses during the last 18 h of culture. The mRNA levels of IL-17A, IL-17F, RORct, IL-1b, IL-18, NLRP3, ASC, and IL-1R1 were detected by quantitative PCR. IL-17A, IL-17F, IL-1b, and IL-18 were tested by ELISA, while the activity of caspase-1 and number of Th17 cells were counted by flow cytometry before/after inhibition of the NLRP3 inflammasome. We found that leptin pushed up the expression of IL-17A, IL-17F, NLRP3, and IL-1b and increased the number of Th17 cells in lupus mice, while the expression of IL-17A, RORct, and IL-1b and the number of Th17 cells were decreased after inhibition of the NLRP3 inflammasome. Leptin promoted the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome.

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Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

Abstract: Circulating Th17 cells were significantly raised in patients with active proliferative LN and showed a significant reduction in responder patients following therapy.

Cited by 10 publications

References 33 publications

Facilitated expansion of Th17 cells in lupus nephritis patients

Facilitated expansion of Th17 cells in lupus nephritis patients

Tris DBA Ameliorates Accelerated and Severe Lupus Nephritis in Mice by Activating Regulatory T Cells and Autophagy and Inhibiting the NLRP3 Inflammasome

Leptin facilitates the differentiation of Th17 cells from MRL/Mp-Fas lpr lupus mice by activating NLRP3 inflammasome

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