The interaction between ischemia–reperfusion and immune responses in the kidney

Jang, Hye Ryoun; Ko, Gang Jee; Wąsowska, Barbara; Rabb, Hamid

doi:10.1007/s00109-009-0491-y

Cited by 185 publications

(160 citation statements)

References 47 publications

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“…Furthermore, APCs increase the expression of costimulatory molecules and migrate to the draining lymph node to activate CD4 + and CD8 + T lymphocytes, thereby contributing to tissue damage. 4 Our group and others have demonstrated the role of different immune cell populations in kidney IRI. [5][6][7][8][9] Recently, an intimate connection between the intestine and the kidneys has been proposed.…”

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confidence: 95%

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

Andrade-Oliveira

Amano

Corrêa-Costa

et al. 2015

Journal of the American Society of Nephrology

390

326

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Short-chain fatty acids (SCFAs) are fermentation end products produced by the intestinal microbiota and have anti-inflammatory and histone deacetylase-inhibiting properties. Recently, a dual relationship between the intestine and kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI model in which the inflammatory process has a detrimental role. We observed that therapy with the three main SCFAs (acetate, propionate, and butyrate) improved renal dysfunction caused by injury. This protection was associated with low levels of local and systemic inflammation, oxidative cellular stress, cell infiltration/activation, and apoptosis. However, it was also associated with an increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and modulated the expression levels of enzymes involved in chromatin modification. In vitro analyses showed that SCFAs modulated the inflammatory process, decreasing the maturation of dendritic cells and inhibiting the capacity of these cells to induce CD4 + and CD8 + T cell proliferation. Furthermore, SCFAs ameliorated the effects of hypoxia in kidney epithelial cells by improving mitochondrial biogenesis. Notably, mice treated with acetate-producing bacteria also had better outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and viability after an injury through modulation of the inflammatory process, most likely via epigenetic modification.

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mentioning

confidence: 95%

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

Andrade-Oliveira

Amano

Corrêa-Costa

et al. 2015

Journal of the American Society of Nephrology

390

326

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“…IRI is a multifactorial process, among which the inflammatory response is an important contributor. 1,2 CD4 + T cell is a key player in the pathogenesis of renal IRI. 3,4 T cell deficiency results in resistance to renal IRI, which can be restored by the adoptive transfer of CD4 + T cells.…”

mentioning

confidence: 99%

Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury

Zhang

Han

Dai

et al. 2016

Journal of the American Society of Nephrology

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Natural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2a in T/NKT cells and found that HIF-2a knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2a knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1 + cell depletion or Fas ligand blockade.Compared with wild-type NKT cells, HIF-2a 2/2 NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2a-dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2a 2/2 NKT cells. Finally, CGS21680 and LPS, an inducer of HIF-2a in endothelium, synergistically reduced renal IRI substantially, but this effect was absent in Mx1-Cre-induced global HIF-2a-knockout mice. Taken together, our results reveal a hypoxia/HIF-2a/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI.

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“…En effet, les lésions d'IR, comme le relargage des DAMP et l'activation endothéliale, favorisent le recrutement et l'activation des monocytes et des cellules dendritiques, ainsi que l'expression des molécules de classe II du complexe majeur d'histocompatibilité (CMH) sur les cellules présentatrices d'antigènes (CPA) [18]. Ces phénomènes accentuent le processus de reconnaissance allogénique caractérisé par : (1) le contact des cellules du greffon avec celles du receveur via la migration des CPA -cellules dendritiques ou macrophages -vers les organes lymphoïdes secondaires, ou (2) les CPA du receveur qui captent les alloantigènes du Les conditions de ces prélèvements sont délétères pour le greffon et pour l'ensemble de l'organisme, en raison essentiellement d'une décharge de catécholamines et de cytokines pro-inflammatoires associée à un état hémodynamique instable [10].…”

Section: Impact De L'ischémie Reperfusion Sur L'alloréactivité Et L'iunclassified

“…Notre unité a montré que l'intensité des lésions d'ischémie induites par une ischémie chaude de 60 min ou une ischémie froide de 24 h (voir Encadré), ou la combinaison des deux, entraîne une élévation de la créatinine durant la première semaine post-reperfusion, en relation avec la sévérité de l'ischémie [15]. Il s'y associe un infiltrat inflammatoire du greffon composé aussi SYNTHÈSE REVUES transplant et les présentent aux lymphocytes T médiateurs d'une réac-tion immunitaire adaptative [1,18]. Ainsi, l'IR constitue un obstacle à l'immunotolérance du greffon via les ligands endogènes libérés par les tissus lésés qui vont activer les TLR (Toll-like receptor) et la réponse immunitaire innée [16].…”

Section: Qualité Du Greffon Et Ischémie Reperfusionunclassified