Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis

Margherita Massa, Maristella Passalia, Silvia Magni Manzoni, Rita Campanelli, Laura Ciardelli, Gisella Puga Yung, Sylvia Kamphuis, Angela Pistorio, Valentina Meli, Alessandro Sette, Berent Prakken, Alberto Martini, Salvatore Albani

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Objective. To identify epitopes on Escherichia coli heat-shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA). Methods. We used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan-HLA-DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells. Sorted cells were then analyzed for the expression of the forkhead box P3 (FoxP3) transcription factor, and their regulatory capacity was tested in coculture assays. Results. T cell responses to E coli HSP dnaJ-derived peptides were eminently proinflammatory. Conversely, peptides derived from human HSP dnaJ induced interleuldn-10 (IL-10) production from SFMCs of patients with oligoarticular JIA. A positive correlation was found between disease with a better prognosis (persistent oligoarticular JIA) and recognition of 3 human HSP dnaJ-derived peptides. The recognition of the human peptide H134-148 also induced a significantly greater amount of IL-10 in patients with persistent oligoarticular JIA than in those with extended oligoarticular JIA (P = 0.0012). Incubation of SFMCs from patients with persistent oligoarticular JIA with this human epitope increased the percentage of Treg cells and FoxP3 expression. It also induced the recovery of suppressor activity by Treg cells. Conclusion. This is the first description of a self-regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis.

Original languageEnglish
Pages (from-to)1648-1657
Number of pages10
JournalArthritis and Rheumatism
Volume56
Issue number5
DOIs
Publication statusPublished - May 2007

Fingerprint

Juvenile Arthritis
Regulatory T-Lymphocytes
Heat-Shock Proteins
Epitopes
Inflammation
Synovial Fluid
Peptides
Escherichia coli Proteins
Forkhead Transcription Factors
T-Lymphocyte Epitopes
HLA-DR Antigens
Coculture Techniques
Cytokines
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis. / Massa, Margherita; Passalia, Maristella; Manzoni, Silvia Magni; Campanelli, Rita; Ciardelli, Laura; Yung, Gisella Puga; Kamphuis, Sylvia; Pistorio, Angela; Meli, Valentina; Sette, Alessandro; Prakken, Berent; Martini, Alberto; Albani, Salvatore.

In: Arthritis and Rheumatism, Vol. 56, No. 5, 05.2007, p. 1648-1657.

Research output: Contribution to journalArticle

@article{6f4a17e4864144cfba40f18cfb0a2f02,
title = "Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis",
abstract = "Objective. To identify epitopes on Escherichia coli heat-shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA). Methods. We used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan-HLA-DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells. Sorted cells were then analyzed for the expression of the forkhead box P3 (FoxP3) transcription factor, and their regulatory capacity was tested in coculture assays. Results. T cell responses to E coli HSP dnaJ-derived peptides were eminently proinflammatory. Conversely, peptides derived from human HSP dnaJ induced interleuldn-10 (IL-10) production from SFMCs of patients with oligoarticular JIA. A positive correlation was found between disease with a better prognosis (persistent oligoarticular JIA) and recognition of 3 human HSP dnaJ-derived peptides. The recognition of the human peptide H134-148 also induced a significantly greater amount of IL-10 in patients with persistent oligoarticular JIA than in those with extended oligoarticular JIA (P = 0.0012). Incubation of SFMCs from patients with persistent oligoarticular JIA with this human epitope increased the percentage of Treg cells and FoxP3 expression. It also induced the recovery of suppressor activity by Treg cells. Conclusion. This is the first description of a self-regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis.",
author = "Margherita Massa and Maristella Passalia and Manzoni, {Silvia Magni} and Rita Campanelli and Laura Ciardelli and Yung, {Gisella Puga} and Sylvia Kamphuis and Angela Pistorio and Valentina Meli and Alessandro Sette and Berent Prakken and Alberto Martini and Salvatore Albani",
year = "2007",
month = "5",
doi = "10.1002/art.22567",
language = "English",
volume = "56",
pages = "1648--1657",
journal = "Arthritis care and research : the official journal of the Arthritis Health Professions Association",
issn = "0893-7524",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis

AU - Massa, Margherita

AU - Passalia, Maristella

AU - Manzoni, Silvia Magni

AU - Campanelli, Rita

AU - Ciardelli, Laura

AU - Yung, Gisella Puga

AU - Kamphuis, Sylvia

AU - Pistorio, Angela

AU - Meli, Valentina

AU - Sette, Alessandro

AU - Prakken, Berent

AU - Martini, Alberto

AU - Albani, Salvatore

PY - 2007/5

Y1 - 2007/5

N2 - Objective. To identify epitopes on Escherichia coli heat-shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA). Methods. We used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan-HLA-DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells. Sorted cells were then analyzed for the expression of the forkhead box P3 (FoxP3) transcription factor, and their regulatory capacity was tested in coculture assays. Results. T cell responses to E coli HSP dnaJ-derived peptides were eminently proinflammatory. Conversely, peptides derived from human HSP dnaJ induced interleuldn-10 (IL-10) production from SFMCs of patients with oligoarticular JIA. A positive correlation was found between disease with a better prognosis (persistent oligoarticular JIA) and recognition of 3 human HSP dnaJ-derived peptides. The recognition of the human peptide H134-148 also induced a significantly greater amount of IL-10 in patients with persistent oligoarticular JIA than in those with extended oligoarticular JIA (P = 0.0012). Incubation of SFMCs from patients with persistent oligoarticular JIA with this human epitope increased the percentage of Treg cells and FoxP3 expression. It also induced the recovery of suppressor activity by Treg cells. Conclusion. This is the first description of a self-regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis.

AB - Objective. To identify epitopes on Escherichia coli heat-shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA). Methods. We used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan-HLA-DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells. Sorted cells were then analyzed for the expression of the forkhead box P3 (FoxP3) transcription factor, and their regulatory capacity was tested in coculture assays. Results. T cell responses to E coli HSP dnaJ-derived peptides were eminently proinflammatory. Conversely, peptides derived from human HSP dnaJ induced interleuldn-10 (IL-10) production from SFMCs of patients with oligoarticular JIA. A positive correlation was found between disease with a better prognosis (persistent oligoarticular JIA) and recognition of 3 human HSP dnaJ-derived peptides. The recognition of the human peptide H134-148 also induced a significantly greater amount of IL-10 in patients with persistent oligoarticular JIA than in those with extended oligoarticular JIA (P = 0.0012). Incubation of SFMCs from patients with persistent oligoarticular JIA with this human epitope increased the percentage of Treg cells and FoxP3 expression. It also induced the recovery of suppressor activity by Treg cells. Conclusion. This is the first description of a self-regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis.

UR - http://www.scopus.com/inward/record.url?scp=34248589182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248589182&partnerID=8YFLogxK

U2 - 10.1002/art.22567

DO - 10.1002/art.22567

M3 - Article

VL - 56

SP - 1648

EP - 1657

JO - Arthritis care and research : the official journal of the Arthritis Health Professions Association

JF - Arthritis care and research : the official journal of the Arthritis Health Professions Association

SN - 0893-7524

IS - 5

ER -