Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 385 - 391 |
| Number of pages | 7 |
| Journal | Journal of the American Society of Nephrology |
| Volume | 27 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2016 |
Cite this
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Myeloperoxidase peptide-based nasal tolerance in experimental ANCA-associated GN. / Gan, Poh Yi; Tan, Diana Shu Yee; Ooi, Joshua; Alikhan, Maliha; Kitching, Arthur Richard; Holdsworth, Stephen Roger.
In: Journal of the American Society of Nephrology, Vol. 27, No. 2, 2016, p. 385 - 391.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Myeloperoxidase peptide-based nasal tolerance in experimental ANCA-associated GN
AU - Gan, Poh Yi
AU - Tan, Diana Shu Yee
AU - Ooi, Joshua
AU - Alikhan, Maliha
AU - Kitching, Arthur Richard
AU - Holdsworth, Stephen Roger
PY - 2016
Y1 - 2016
N2 - Less toxic treatment options for patients with myeloperoxidase (MPO)-ANCA-associated GN are needed. Using an established murine model of focal necrotizing GN mediated by autoimmunity to MPO (autoimmune anti-MPO GN), we assessed the capacity for nasal tolerance induced by nasal insufflation of the immunodominant nephritogenic MPO peptide (MPO409-428) to attenuate this disease. Compared with mice that received an irrelevant immunodominant ovalbumin (OVA) peptide, OVA323-339, mice that received MPO409-428 were protected from the development of humoral and cell-mediated autoimmunity to full-length MPO and the development of GN. In mice with established anti-MPO autoimmunity, nasal insufflation of MPO409-428 as a therapeutic attenuated anti-MPO GN. To investigate the nature of this induced tolerance, we isolated CD4+ T cells from the upper airway draining lymph nodes of both OVA323-339- and MPO409-428-tolerized mice. Adoptive transfer of CD4+ T cells from MPO409-428- but not OVA323-339-tolerized mice to animals with established anti-MPO autoimmunity attenuated the subsequent development of GN, confirming that the immunosuppression induced by these T cells is antigen specific. Ex vivo studies showed that nasal tolerance to MPO is mediated by both conventional and induced T regulatory cells. The strong homology between the pathogenic human MPO B cell epitope recognized by ANCA in patients with acute vasculitis and the nephritogenic murine T cell MPO epitope emphasizes the clinical relevance of this study.
AB - Less toxic treatment options for patients with myeloperoxidase (MPO)-ANCA-associated GN are needed. Using an established murine model of focal necrotizing GN mediated by autoimmunity to MPO (autoimmune anti-MPO GN), we assessed the capacity for nasal tolerance induced by nasal insufflation of the immunodominant nephritogenic MPO peptide (MPO409-428) to attenuate this disease. Compared with mice that received an irrelevant immunodominant ovalbumin (OVA) peptide, OVA323-339, mice that received MPO409-428 were protected from the development of humoral and cell-mediated autoimmunity to full-length MPO and the development of GN. In mice with established anti-MPO autoimmunity, nasal insufflation of MPO409-428 as a therapeutic attenuated anti-MPO GN. To investigate the nature of this induced tolerance, we isolated CD4+ T cells from the upper airway draining lymph nodes of both OVA323-339- and MPO409-428-tolerized mice. Adoptive transfer of CD4+ T cells from MPO409-428- but not OVA323-339-tolerized mice to animals with established anti-MPO autoimmunity attenuated the subsequent development of GN, confirming that the immunosuppression induced by these T cells is antigen specific. Ex vivo studies showed that nasal tolerance to MPO is mediated by both conventional and induced T regulatory cells. The strong homology between the pathogenic human MPO B cell epitope recognized by ANCA in patients with acute vasculitis and the nephritogenic murine T cell MPO epitope emphasizes the clinical relevance of this study.
UR - http://www.ncbi.nlm.nih.gov/pubmed/26047792
U2 - 10.1681/ASN.2015010089
DO - 10.1681/ASN.2015010089
M3 - Article
VL - 27
SP - 385
EP - 391
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
SN - 1046-6673
IS - 2
ER -