Distinct expression of interleukin 17, tumor necrosis factor α, transforming growth factor β, and forkhead box P3 in acute rejection after kidney transplantation

Abstract

The kidney transplant is the main therapeutic alternative for end-stage kidney disease, and rejection is a major complication. The expression of proinflammatory cytokines is related to graft loss, whereas anti-inflammatory cytokines are associated with graft protection. The objective of this study is to evaluate the "in situ" expression of cytokines T helper 1 (tumor necrosis factor α [TNF-α]), T helper 17 (interleukin 17 [IL-17]), and regulatory T cell (transforming growth factor β [TGF-β]) and the expression of forkhead box P3 (FoxP3) in allograft kidney. We evaluated in situ expression of cytokines in allograft kidney under rejection process by indirect immunohistochemistry. Eighteen renal graft biopsies were from patients with episodes of rejection. The in situ expression of IL-17, TNF-α, and TGF-β was significantly higher in patients with acute rejection when compared with the control group. In contrast, analysis of FoxP3 expression showed few positive cells in patients with acute rejection compared with the control group. The results suggest that the expression of proinflammatory cytokines (IL-17 and TNF-α) contributes to the mechanisms of kidney transplant rejection. The increase in TGF-β expression might be an attempt to establish a process of immunoregulation or even to induce higher production of IL-17. The last hypothesis is supported by the observation of a reduced expression of FoxP3 and elevated levels of IL-17.

16th IHIW: Anti‐HLA alloantibodies of the of IgA isotype in re‐transplant candidates

“…It also remains unclear why certain patients produce anti‐HLA antibodies of the IgA isotype at all. IgA class switch is enhanced by TGFβ (Coffman et al ., ), which is produced locally during kidney allograft rejection (de Menezes Neves et al ., ). In this regard, it would have been interesting to know whether patients with anti‐HLA antibodies of the IgA isotype might have undergone less often a transplantectomy in contrast to those without.…”

PARP Inhibition Attenuates Acute Kidney Allograft Rejection by Suppressing Cell Death Pathways and Activating PI-3K-Akt Cascade

“…Causes may be ischemia-reperfusion induced oxidative stress, inflammatory cytokines or monocyte/macrophage produced reactive oxygen species [3], [6], [40]. The critical role of oxidative stress in rejection is supported by the observations that N-acetylcysteine prevents early rejection in animal models [41].…”

“…Rejection is often characterized and mediated by the presence of at least 4 types of committed helper T cells (T helper (Th)1, Th2, Th17, and regulatory T cells) in the interstitial, tubular, and glomerular compartments [1], [2]. The presence of these cells is often associated with vasculitis, deposition of immunoglobulins in peritubular capillaries [3]. An activation of the complement cascade [4] and the presence of proinflammatory cytokines (e.g.…”

“…TNF-α and IL-17) may also be involved. Anti-inflammatory cytokines, such as TGF-β, the transcription factor of regulatory T cells and FoxP3 on the other hand facilitate better transplant survival [3]. Allograft damage may be also caused by leukocyte infiltration, recruitment of neutrophils and monocytes on activated endothelial cells contributing to tubular interstitial inflammation and oxidative stress.…”

The Importance of C4d in Biopsies of Kidney Transplant Recipients

“…A study from our group in patients with acute rejection showed that cases of cellular rejection have minimal immunostaining for C4d compared to cases of humoral rejection [23]. The minimal immunostaining for C4d in cellular rejection probably occurs through the activated via the mannose-binding lectin cascade [24, 25]; although complement factors activation on T-cell responses are mediated not only via specific signalling events in the T cell itself but also indirectly via alterations in antigen presenting cells and other cells that modulate T-cell activity [20].…”