Regulatory T cells and minimal change nephropathy: In the midst of a complex network

R. Bertelli, A. Bonanni, A. Di Donato, M. Cioni, P. Ravani, G. M. Ghiggeri

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Minimal change nephrosis (MCN) is an important cause of morbidity in children. In spite of successful therapies having been developed in the last three decades, most aspects related to pathogenesis still remain poorly defined. Evolution in basic immunology and results deriving from animal models of the disease suggest a complex interaction of factors and cells starting from activation of innate immunity and continuing with antigen presentation. Oxidants, CD80 and CD40/CD40L have probably a relevant role at the start. Studies in animal models and in human beings also suggest the possibility that the same molecules (i.e. CD80, CD40) are expressed by podocytes under inflammatory stimuli, representing a direct potential mechanism for proteinuria. B and T cells could play a relevant role this contest. Implication of B cells is suggested indirectly by studies utilizing anti-CD20 monoclonal antibodies as the main therapy. The role of regulatory T cells (Tregs) is supported mainly by results in animal models of nephrotic syndrome (i.e. adriamycin, puromycin, lipopolysaccharide), showing a protective effect of direct Treg infusion or stimulation by interleukin 2 (IL-2). Limited studies have also shown reduced amounts of circulating Tregs in patients with active MCN cells. The route from bench to bedside would be reduced if results from animal models were confirmed in human pathology. The expansion of Tregs with recombinant IL-2 and new anti-CD20 monoclonal antibodies is the beginning. Blocking antigen-presenting cells with cytotoxic T lymphocyte antigen (CTLA-4)-Ig fusion molecules inhibiting CD80 and/or with blockers of CD40-CD40 ligand interaction represent potential new approaches. The hope is that evolution in therapies of MCN could fill a gap lasting 30 years.

Original languageEnglish
Pages (from-to)166-174
Number of pages9
JournalClinical and Experimental Immunology
Volume183
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

Fingerprint

Nephrosis
Lipoid Nephrosis
Regulatory T-Lymphocytes
CD40 Ligand
Animal Models
Interleukin-2
B-Lymphocytes
Monoclonal Antibodies
CTLA-4 Antigen
Animal Disease Models
Puromycin
Podocytes
Antigen Presentation
Nephrotic Syndrome
Antigen-Presenting Cells
Allergy and Immunology
Proteinuria
Innate Immunity
Oxidants
Cell Communication

Keywords

  • IL-2
  • LPS nephropathy
  • Minimal change nephropathy
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Regulatory T cells and minimal change nephropathy : In the midst of a complex network. / Bertelli, R.; Bonanni, A.; Di Donato, A.; Cioni, M.; Ravani, P.; Ghiggeri, G. M.

In: Clinical and Experimental Immunology, Vol. 183, No. 2, 01.02.2016, p. 166-174.

Research output: Contribution to journalArticle

@article{9a0b89b98875477d9c105391a061f765,
title = "Regulatory T cells and minimal change nephropathy: In the midst of a complex network",
abstract = "Minimal change nephrosis (MCN) is an important cause of morbidity in children. In spite of successful therapies having been developed in the last three decades, most aspects related to pathogenesis still remain poorly defined. Evolution in basic immunology and results deriving from animal models of the disease suggest a complex interaction of factors and cells starting from activation of innate immunity and continuing with antigen presentation. Oxidants, CD80 and CD40/CD40L have probably a relevant role at the start. Studies in animal models and in human beings also suggest the possibility that the same molecules (i.e. CD80, CD40) are expressed by podocytes under inflammatory stimuli, representing a direct potential mechanism for proteinuria. B and T cells could play a relevant role this contest. Implication of B cells is suggested indirectly by studies utilizing anti-CD20 monoclonal antibodies as the main therapy. The role of regulatory T cells (Tregs) is supported mainly by results in animal models of nephrotic syndrome (i.e. adriamycin, puromycin, lipopolysaccharide), showing a protective effect of direct Treg infusion or stimulation by interleukin 2 (IL-2). Limited studies have also shown reduced amounts of circulating Tregs in patients with active MCN cells. The route from bench to bedside would be reduced if results from animal models were confirmed in human pathology. The expansion of Tregs with recombinant IL-2 and new anti-CD20 monoclonal antibodies is the beginning. Blocking antigen-presenting cells with cytotoxic T lymphocyte antigen (CTLA-4)-Ig fusion molecules inhibiting CD80 and/or with blockers of CD40-CD40 ligand interaction represent potential new approaches. The hope is that evolution in therapies of MCN could fill a gap lasting 30 years.",
keywords = "IL-2, LPS nephropathy, Minimal change nephropathy, Regulatory T cells",
author = "R. Bertelli and A. Bonanni and {Di Donato}, A. and M. Cioni and P. Ravani and Ghiggeri, {G. M.}",
year = "2016",
month = "2",
day = "1",
doi = "10.1111/cei.12675",
language = "English",
volume = "183",
pages = "166--174",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Regulatory T cells and minimal change nephropathy

T2 - In the midst of a complex network

AU - Bertelli, R.

AU - Bonanni, A.

AU - Di Donato, A.

AU - Cioni, M.

AU - Ravani, P.

AU - Ghiggeri, G. M.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Minimal change nephrosis (MCN) is an important cause of morbidity in children. In spite of successful therapies having been developed in the last three decades, most aspects related to pathogenesis still remain poorly defined. Evolution in basic immunology and results deriving from animal models of the disease suggest a complex interaction of factors and cells starting from activation of innate immunity and continuing with antigen presentation. Oxidants, CD80 and CD40/CD40L have probably a relevant role at the start. Studies in animal models and in human beings also suggest the possibility that the same molecules (i.e. CD80, CD40) are expressed by podocytes under inflammatory stimuli, representing a direct potential mechanism for proteinuria. B and T cells could play a relevant role this contest. Implication of B cells is suggested indirectly by studies utilizing anti-CD20 monoclonal antibodies as the main therapy. The role of regulatory T cells (Tregs) is supported mainly by results in animal models of nephrotic syndrome (i.e. adriamycin, puromycin, lipopolysaccharide), showing a protective effect of direct Treg infusion or stimulation by interleukin 2 (IL-2). Limited studies have also shown reduced amounts of circulating Tregs in patients with active MCN cells. The route from bench to bedside would be reduced if results from animal models were confirmed in human pathology. The expansion of Tregs with recombinant IL-2 and new anti-CD20 monoclonal antibodies is the beginning. Blocking antigen-presenting cells with cytotoxic T lymphocyte antigen (CTLA-4)-Ig fusion molecules inhibiting CD80 and/or with blockers of CD40-CD40 ligand interaction represent potential new approaches. The hope is that evolution in therapies of MCN could fill a gap lasting 30 years.

AB - Minimal change nephrosis (MCN) is an important cause of morbidity in children. In spite of successful therapies having been developed in the last three decades, most aspects related to pathogenesis still remain poorly defined. Evolution in basic immunology and results deriving from animal models of the disease suggest a complex interaction of factors and cells starting from activation of innate immunity and continuing with antigen presentation. Oxidants, CD80 and CD40/CD40L have probably a relevant role at the start. Studies in animal models and in human beings also suggest the possibility that the same molecules (i.e. CD80, CD40) are expressed by podocytes under inflammatory stimuli, representing a direct potential mechanism for proteinuria. B and T cells could play a relevant role this contest. Implication of B cells is suggested indirectly by studies utilizing anti-CD20 monoclonal antibodies as the main therapy. The role of regulatory T cells (Tregs) is supported mainly by results in animal models of nephrotic syndrome (i.e. adriamycin, puromycin, lipopolysaccharide), showing a protective effect of direct Treg infusion or stimulation by interleukin 2 (IL-2). Limited studies have also shown reduced amounts of circulating Tregs in patients with active MCN cells. The route from bench to bedside would be reduced if results from animal models were confirmed in human pathology. The expansion of Tregs with recombinant IL-2 and new anti-CD20 monoclonal antibodies is the beginning. Blocking antigen-presenting cells with cytotoxic T lymphocyte antigen (CTLA-4)-Ig fusion molecules inhibiting CD80 and/or with blockers of CD40-CD40 ligand interaction represent potential new approaches. The hope is that evolution in therapies of MCN could fill a gap lasting 30 years.

KW - IL-2

KW - LPS nephropathy

KW - Minimal change nephropathy

KW - Regulatory T cells

UR - http://www.scopus.com/inward/record.url?scp=84954487531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954487531&partnerID=8YFLogxK

U2 - 10.1111/cei.12675

DO - 10.1111/cei.12675

M3 - Article

AN - SCOPUS:84954487531

VL - 183

SP - 166

EP - 174

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

IS - 2

ER -