| Addition of an indoleamine 2,3,-dioxygenase inhibitor to B cell-depletion therapy blocks autoreactive B cell activation and recurrence of arthritis in K/BxN mice. | |
| | |
MedLine Citation:
|
PMID: 22294267 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: To define the role of indoleamine 2,3-dioxygenase (IDO) in driving pathogenic B cell responses that lead to arthritis and to determine if inhibitors of the IDO pathway can be used in conjunction with therapeutic B cell depletion to prevent the reemergence of autoantibodies and arthritis following reconstitution of the B cell repertoire. METHODS: Immunoglobulin-transgenic mice were treated with the IDO inhibitor 1-methyltryptophan (1-MT) and monitored for the extent of autoreactive B cell activation. Arthritic K/BxN mice were treated with B cell depletion alone or in combination with 1-MT. Mice were monitored for the presence of autoantibody-secreting cells, inflammatory cytokines, and joint inflammation. RESULTS: Treatment with 1-MT did not affect the initial activation or survival of autoreactive B cells, but it did inhibit their ability to differentiate into autoantibody-secreting cells. Treatment with anti-CD20 depleted the B cell repertoire and attenuated arthritis symptoms; however, the arthritis symptoms rapidly returned as B cells repopulated the repertoire. Administration of 1-MT prior to B cell repopulation prevented the production of autoantibodies and inflammatory cytokines and flare of arthritis symptoms. CONCLUSION: IDO activity is essential for the differentiation of autoreactive B cells into antibody-secreting cells, but it is not necessary for their initial stages of activation. Addition of 1-MT to therapeutic B cell depletion prevents the differentiation of autoantibody-secreting cells and the recurrence of autoimmune arthritis following reconstitution of the B cell repertoire. These data suggest that IDO inhibitors could be used in conjunction with B cell depletion as an effective cotherapeutic strategy in the treatment of rheumatoid arthritis. |
| | |
Authors:
|
Elizabeth Pigott; Laura Mandik-Nayak |
Related Documents
:
|
2823717 - Cell-cycle dependence of dolichyl phosphate biosynthesis. 2441047 - Novel nucleolar antigens in autoimmune disease. 8380637 - Regulation of cell cycle progression and nuclear affinity of the retinoblastoma protein... 11341787 - Frap-p70s6k signaling is required for pancreatic cancer cell proliferation. 221667 - Unstable resistance of g mouse fibroblasts to ecotropic murine leukemia virus infection. 333447 - Cell cycle of saccharomycescerevisiae in populations growing at different rates. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: Arthritis and rheumatism Volume: 64 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2012 Jul |
Date Detail:
|
Created Date: 2012-06-28 Completed Date: 2012-09-14 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
|
Languages: eng Pagination: 2169-78 Citation Subset: AIM; IM |
Copyright Information:
|
Copyright © 2012 by the American College of Rheumatology. |
Affiliation:
|
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Arthritis, Experimental / drug therapy, immunology, therapy* Autoantibodies / immunology* B-Lymphocytes / immunology*, pathology Cell Differentiation Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors* Lymphocyte Depletion / methods* Mice Mice, Transgenic Recurrence / prevention & control Tryptophan / analogs & derivatives*, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
|
5-R01-AR-057847-01/AR/NIAMS NIH HHS; R01 AR057847/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/1-methyltryptophan; 0/Autoantibodies; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 73-22-3/Tryptophan |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Pre-neoplastic lesion, mucin-depleted foci, reveals de novo high-grade dysplasia in rat...
Next Document: Virtual temporal bone dissection system: OSU virtual temporal bone system: development and testing.