The requirement of natural killer T-cells in tolerogenic APCs-mediated suppression of collagen-induced arthritis

Jung, Seonghoon; Park, Yoon Kyung; Shin, Jung Hoon; Lee, Hyunji; Kim, Soo Young; Lee, Gap Ryol; Park, Seho

doi:10.3858/emm.2010.42.8.055

Cited by 7 publications

(8 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, a previous study indicated that deletion of furin in CD4+ cells was found to impair T cell function by altering the production of TGFβ (15). Indeed, TGFβ promotes naive T cells to a Treg cell phenotype (35), and TGFβ‐secreting cells suppress the development and severity of CIA (36). Therefore, our observations raise the hypothesis that exogenous furin might also affect the processing of TGFβ, resulting in protection against arthritis.…”

Section: Discussionmentioning

confidence: 99%

Protective role of systemic furin in immune response–induced arthritis

Lin

Kioon

Lalou

et al. 2012

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis (RA) is an autoimmune joint disease associated with chronic inflammation of the synovium that causes profound damage of joints. Inflammation results in part from the influx of immune cells secreting inflammatory cytokines and the reduction in the number of Treg cells. We undertook this study to assess the effect of furin, a proteinase implicated in the proteolytic activity of various precursor proteins and involved in the regulation of both proteinase maturation and immune cells, in an experimental model of RA.Methods. The effect of furin and its inhibitor ␣1-PDX was tested in mice with collagen-induced arthritis (CIA). Joints were processed for histology and protein expression. Levels of cytokines were measured in joint tissue, and Treg cell numbers were measured in spleens.Results. Furin expression and activity were high in the synovial pannus in RA patients and mice with CIA. Systemic administration of furin prevented increases in the arthritis score, joint destruction, and bone loss, in contrast to systemic administration of the furin inhibitor ␣1-PDX, which enhanced these parameters. By preventing the development of synovial pannus, furin reduced the expression of metalloproteinases in the joints. In contrast, ␣1-PDX enhanced synovial proliferation and the expression and activity of matrix metalloproteinases. Furthermore, furin reversed the local Th1/Th2 balance and restored the number of Treg cells in the spleen, indicating mediation by immune cells.Conclusion. These findings show the protective role of exogenous furin against RA, mediated by an immune response. The data suggest the potential therapeutic use of furin or its derivatives in autoimmune diseases including RA.

show abstract

Section: Discussionmentioning

confidence: 99%

Protective role of systemic furin in immune response–induced arthritis

Lin

Kioon

Lalou

et al. 2012

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Splenic dendritic and macrophage APCs however showed reduced expression of CD40, CD80 and CD86 costimulatory molecules (Miellot-Gafsou et al, 2010). In addition, Jung et al (2010) have demonstrated a more subtle late regulatory role for NKT cells in tolerogenic DC (Tol-DC) mediated suppression of CIA. Thus TGF-ϐ induced, peritoneal exudate cell (PEC)-derived Tol-DC from CD1d + / -but not CD1d -/ -mice could suppress the incidence, onset and severity of CIA when administered on day 28.…”

Section: Dba1/j Micementioning

confidence: 99%

“…IL-17 producing iNKT cells have been noted to steadily increase in numbers until the very late stages of disease in DBA/1 mice (Jung et al, 2009) and anti-CD1d administered to C57BL/6 mice on day 21 results in disease amelioration (Chiba et al, 2005). In addition, Jung et al demonstrated that CD1d + / -but not CD1d -/ -Tol-DC could suppress CIA in DBA/1 mice when administered as late as day 28 (Jung et al, 2010). So how do iNKT cells influence the immune pathogenesis of CIA?…”

Section: Lessons Learnt From Animal Models Of Autoimmune Arthritismentioning

confidence: 99%

“…It is unclear which particular iNKT cell subset is responsible for exacerbating disease, whether the same subsets are pathogenic at different stages or even whether some subsets play a protective role a s s u g g e s t e d b y J u n g e t a l . ' s T o l -D C experimental model (Jung et al, 2010). Neither do we know how iNKT cells become activated or the mechanism(s) whereby they skew the phenotypic immune response to CII.…”

Section: Lessons Learnt From Animal Models Of Autoimmune Arthritismentioning

confidence: 99%

See 1 more Smart Citation

Invariant Natural Killer T Cells in Rheumatoid Arthritis and Other Inflammatory Arthritides

Sowden¹,

Ng²

2012

Rheumatoid Arthritis - Etiology, Consequences and Co-Morbidities

View full text Add to dashboard Cite

“…We have previously reported that TGFβ-treated tolerogenic pMφ from CD1d +/− mice, but not from CD1d KO (iNKT cell-deficient) mice, can facilitate APC-mediated suppression of CIA ( 14 ). In this study, we expanded these initial findings and investigated capabilities of pMφ.…”

Section: Introductionmentioning

confidence: 99%

CD1d deficiency limits tolerogenic properties of peritoneal macrophages

et al. 2021

Self Cite

View full text Add to dashboard Cite

Invariant natural killer T (iNKT) cells are involved in various autoimmune diseases. Although iNKT cells are arthritogenic, transforming growth factor beta (TGFβ)-treated tolerogenic peritoneal macrophages (Tol-pMφ) from wild-type (WT) mice are more tolerogenic than those from CD1d knock-out iNKT cell-deficient mice in a collagen-induced arthritis (CIA) model. The underlying mechanism by which pMφ can act as tolerogenic antigen presenting cells (APCs) is currently unclear. To determine cellular mechanisms underlying CD1d-dependent tolerogenicity of pMφ, in vitro and in vivo characteristics of pMφ were investigated. Unlike dendritic cells or splenic Mφ, pMφ from CD1d +/− mice showed lower expression levels of costimulatory molecule CD86 and produced lower amounts of inflammatory cytokines upon lipopolysaccharide (LPS) stimulation compared to pMφ from CD1d-deficient mice. In a CIA model of CD1d-deficient mice, adoptively transferred pMφ from WT mice reduced the severity of arthritis. However, pMφ from CD1d-deficient mice were unable to reduce the severity of arthritis. Hence, the tolerogenicity of pMφ is a cell-intrinsic property that is probably confer-red by iNKT cells during pMφ development rather than by interactions of pMφ with iNKT cells during antigen presentation to cognate T cells.

show abstract

The requirement of natural killer T-cells in tolerogenic APCs-mediated suppression of collagen-induced arthritis

Cited by 7 publications

References 42 publications

Protective role of systemic furin in immune response–induced arthritis

Protective role of systemic furin in immune response–induced arthritis

Invariant Natural Killer T Cells in Rheumatoid Arthritis and Other Inflammatory Arthritides

CD1d deficiency limits tolerogenic properties of peritoneal macrophages

Contact Info

Product

Resources

About