The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3+ cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p < 0.01). Most FOXP3 + cells were CD4 + (96%); a minority expressed CD8. FOXP3 + CD4 + cells were concentrated in the tubules (p < 0.001), suggesting a selective attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3 + correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3 + cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined.

Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation.

BackgroundTo investigate gene expression of podocyte-specific proteins in urine of diabetes and prediabetes subjects and the association of these proteins with albuminuria.MethodsFifteen controls, 19 prediabetes, and 67 diabetes subjects were included. Messenger RNA of nephrin, podocin, podocalyxin, synaptopodin, TRPC6, alpha-actinin-4, and TGF-β1 were measured using RT-PCR. Podocyte marker expression was correlated with albuminuria, glycemic control, and renal function. The diagnostic performance of the genes used to detect increased albuminuria was assessed using ROC curves and Poisson regressions.ResultsPodocyte marker expression was significantly higher in diabetic subjects. Urinary nephrin was correlated with increasing levels of albuminuria; risk of albuminuria increased by 20% for every one-unit increase in the log10 of nephrin mRNA. Nephrinuria was found in 53%, 71%, and 90% of normo-, micro-, and macroalbuminuric diabetes subjects, respectively (p = 0.023). Urinary nephrin, podocalyxin, TRPC6, podocin, and alpha actinin-4 were correlated with glycemic control and albuminuria but not with renal function.ConclusionsDiabetes subjects had higher urinary mRNA levels of podocyte proteins than nondiabetic subjects, even the normoalbuminuric patients. Nephrinuria was correlated with diabetic nephrophathy stage and predicted pathological albuminuria. Urinary mRNA levels of podocyte markers of prediabetic subjects did not differ from controls.