T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

Liappas, Georgios; Gónzalez-Mateo, Guadalupe Tirma; Majano, Pedro L.; Tomero, José Antonio Sánchez; Ruíz-Ortega, Marta; Rodrigues‐Díez, Raquel; Martı́n, Pilar; Sánchez-Díaz, Raquel; Selgas, Rafael; López–Cabrera, Manuel; Peralta, Abelardo Aguilera

doi:10.1155/2015/416480

Cited by 18 publications

(22 citation statements)

References 80 publications

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“…Besides components of the innate immunity, more recent studies performed using murine models demonstrated a main role of T helper 1 (Th1) cell response and of T lymphocytes expressing IL17A [ 19 – 21 ]. In these conditions, the presence of IL-6 is particularly relevant since it may shape the immune response in subacute-chronic conditions.…”

Section: Cellular Players Of Peritoneal Fibrosismentioning

confidence: 99%

“…In these conditions, the presence of IL-6 is particularly relevant since it may shape the immune response in subacute-chronic conditions. IL-6, in combination with TGF- β , is the main cytokine involved in the T helper 17/regulatory T (Th17/Treg) balance [ 21 ]. The predominance of IL-6 favors the generation of Th-17 lymphocytes, which produce inflammatory cytokines.…”

Section: Cellular Players Of Peritoneal Fibrosismentioning

confidence: 99%

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Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis

Strippoli

Moreno-Vicente

Battistelli

et al. 2016

Stem Cells International

111

136

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Peritoneal dialysis is a form of renal replacement alternative to the hemodialysis. During this treatment, the peritoneal membrane acts as a permeable barrier for exchange of solutes and water. Continual exposure to dialysis solutions, as well as episodes of peritonitis and hemoperitoneum, can cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy, eventually leading to discontinuation of the peritoneal dialysis. Among the different events controlling this pathological process, epithelial to mesenchymal transition of mesothelial cells plays a main role in the induction of fibrosis and in subsequent functional deterioration of the peritoneal membrane. Here, the main extracellular inducers and cellular players are described. Moreover, signaling pathways acting during this process are elucidated, with emphasis on signals delivered by TGF-β family members and by Toll-like/IL-1β receptors. The understanding of molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane.

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Section: Cellular Players Of Peritoneal Fibrosismentioning

confidence: 99%

Section: Cellular Players Of Peritoneal Fibrosismentioning

confidence: 99%

Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis

Strippoli

Moreno-Vicente

Battistelli

et al. 2016

Stem Cells International

111

136

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“…[15][16][17] Thus, chronic inflammatory damage of the peritoneal membrane can be modulated, at least in part, through regulation of the Th17/Treg balance. 18 Other cytokines are linked to specific PD-associated patient subgroups and characteristics. The chemokine CCL18 (also known as PARC, DC-CK1 and MIP-4) had originally been described to be predictive of encapsulating peritoneal sclerosis (EPS), but this finding was not confirmed by recent studies.…”

Section: Biomarker Research In the Context Of Chronic Peritoneal Inflmentioning

confidence: 99%

Biomarker research to improve clinical outcomes of peritoneal dialysis: consensus of the European Training and Research in Peritoneal Dialysis (EuTRiPD) network

Aufricht

Beelen

Eberl

et al. 2017

Kidney International

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Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide personalized interventions that may improve clinical outcome in the individual patient. In this consensus article, members of the European Training and Research in Peritoneal Dialysis Network (EuTRiPD) review the current status of biomarker research in PD and suggest a selection of biomarkers that can be relevant to the care of PD patients and that are directly accessible in PD effluents. Currently used biomarkers such as interleukin-6, interleukin-8, ex vivo-stimulated interleukin-6 release, cancer antigen-125, and advanced oxidation protein products that were collected through a Delphi procedure were first triaged for inclusion as surrogate endpoints in a clinical trial. Next, novel biomarkers were selected as promising candidates for proof-of-concept studies and were differentiated into inflammation signatures (including interleukin-17, M/M macrophages, and regulatory T cell/T helper 17), mesothelial-to-mesenchymal transition signatures (including microRNA-21 and microRNA-31), and signatures for senescence and inadequate cellular stress responses. Finally, the need for defining pathogen-specific immune fingerprints and phenotype-associated molecular signatures utilizing effluents from the clinical cohorts of PD patients and "omics" technologies and bioinformatics-biostatistics in future joint-research efforts was expressed. Biomarker research in PD offers the potential to develop valuable tools for improving patient management. However, for all biomarkers discussed in this consensus article, the association of biological rationales with relevant clinical outcomes remains to be rigorously validated in adequately powered, prospective, independent clinical studies.

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“…However, it is important to know that TGFβ is involved in the development and function of regulatory T cells (Tregs) [142][143][144], as adult mice deficient in TGFβ signaling exhibit a defective Treg phenotype with normal numbers, decreased suppressive function, and an incomplete TCR repertoire [145][146][147][148]. Tregs cells are extremely important for the maintenance of the peritoneal protection during PD [149], so treatments intended to block TGF-β signaling should take into account the complete cytokine environment and consider this side effect.…”

Section: Transforming Growth Factor (Tgf)-βmentioning

confidence: 99%

Angiogenesis and Lymphangiogenesis in Peritoneal Dialysis

Gónzalez-Mateo¹,

Pascual-Antón²,

Carrasco³

et al. 2018

Aspects in Dialysis

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The ultrafiltration failure during peritoneal dialysis (PD) is related to inflammatory responses induced by bio-incompatible PD fluids, which may lead to deterioration of peritoneal membrane (PM) function. Mesothelial cells, lymphocytes, macrophages and other cell types present in the peritoneal cavity are stimulated to produce cytokines and growth factors that promote pathological processes. Due to these factors, blood and lymphatic vessels proliferate and could be responsible for hyperfiltration and PM failure type III and IV. Vessels proliferation may be related to fibrosis, being the cause and/or effect of the mesenchymal conversion of different cell types such as mesothelial (MMT), bone marrow-derived (fibrocytes) or endothelial (vascular-and lymph-endo-MT) cells. Lymphangiogenesis in PD is a poorly analysed process; however, its contribution to peritoneal function disorders has been recently recognized. VEGF production is associated with blood and lymphatic vessels proliferation, while specifically lymphangiogenesis is mainly regulated by VEGF-C and VEGF-D. Excessive lymphatic fluid drainage from the abdominal cavity may be related with macromolecule and isosmotic solutions reuptake and convective reabsorption of solutes that were cleared from plasma by diffusion. Some drugs have been shown to modulate tissue fibrosis, MMT, EndoMT, angiogenesis and lymphangiogenesis and could represent interesting therapeutic strategies to protect the PM.

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T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

Cited by 18 publications

References 80 publications

Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis

Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis

Biomarker research to improve clinical outcomes of peritoneal dialysis: consensus of the European Training and Research in Peritoneal Dialysis (EuTRiPD) network

Angiogenesis and Lymphangiogenesis in Peritoneal Dialysis

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