Amelioration of Experimental Autoimmune Encephalomyelitis by the Quinoline-3-Carboxamide Paquinimod (ABR-215757): Reduced Priming of Proinflammatory Effector CD4(+) T Cells.
(2013) In American Journal of Pathology 182(5). p.1671-1680- Abstract
- Quinoline-3-carboxamide compounds (Q compounds) have demonstrated efficacy in treating autoimmune disease in both humans and mice. However, the mode of action of these compounds is poorly understood. Here, we show that preventive treatment with the Q compound paquinimod (ABR-215757) during the first 5 days after induction of experimental autoimmune encephalomyelitis is sufficient to significantly ameliorate disease symptoms. Parallel cell-depletion experiments demonstrated that Ly6C(hi) inflammatory monocytes play an essential role in this phase. The paquinimod-induced amelioration correlated with reduced priming of antigen-specific CD4(+) T cells and reduced frequency of IFN-γ- and IL-17-producing cells in draining lymph nodes.... (More)
- Quinoline-3-carboxamide compounds (Q compounds) have demonstrated efficacy in treating autoimmune disease in both humans and mice. However, the mode of action of these compounds is poorly understood. Here, we show that preventive treatment with the Q compound paquinimod (ABR-215757) during the first 5 days after induction of experimental autoimmune encephalomyelitis is sufficient to significantly ameliorate disease symptoms. Parallel cell-depletion experiments demonstrated that Ly6C(hi) inflammatory monocytes play an essential role in this phase. The paquinimod-induced amelioration correlated with reduced priming of antigen-specific CD4(+) T cells and reduced frequency of IFN-γ- and IL-17-producing cells in draining lymph nodes. Importantly, the treatment did not inhibit T-cell division per se. In mice with established experimental autoimmune encephalomyelitis, the numbers of Ly6C(hi) CD115(+) inflammatory monocytes and CD11b(+)CD11c(+) dendritic cells (DCs) were reduced in spleen, but not in bone marrow or draining lymph nodes of treated mice. Inflammatory monocyte-derived DCs and CD4(+) T cells were also reduced in the brain. In contrast, there was no decrease in DC subsets previously shown to be critical for effector CD4(+) T-cell development in lymph nodes. Taken together, these data indicate that preventive treatment with paquinimod ameliorates experimental autoimmune encephalomyelitis by reducing effector T-cell priming and, on prolonged treatment, displays a selective effect by decreasing distinct subpopulations of splenic CD11b(+) myeloid cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3628026
- author
- Helmersson, Sofia LU ; Sundstedt, Anette ; Deronic, Adnan LU ; Leanderson, Tomas LU and Ivars, Fredrik LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Pathology
- volume
- 182
- issue
- 5
- pages
- 1671 - 1680
- publisher
- American Society for Investigative Pathology
- external identifiers
-
- wos:000318534100022
- pmid:23506849
- scopus:84876572127
- ISSN
- 1525-2191
- DOI
- 10.1016/j.ajpath.2013.01.032
- language
- English
- LU publication?
- yes
- id
- 07937b67-a901-465e-b1a6-df6701b395ec (old id 3628026)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23506849?dopt=Abstract
- date added to LUP
- 2016-04-01 10:12:12
- date last changed
- 2022-04-04 03:25:28
@article{07937b67-a901-465e-b1a6-df6701b395ec,
abstract = {{Quinoline-3-carboxamide compounds (Q compounds) have demonstrated efficacy in treating autoimmune disease in both humans and mice. However, the mode of action of these compounds is poorly understood. Here, we show that preventive treatment with the Q compound paquinimod (ABR-215757) during the first 5 days after induction of experimental autoimmune encephalomyelitis is sufficient to significantly ameliorate disease symptoms. Parallel cell-depletion experiments demonstrated that Ly6C(hi) inflammatory monocytes play an essential role in this phase. The paquinimod-induced amelioration correlated with reduced priming of antigen-specific CD4(+) T cells and reduced frequency of IFN-γ- and IL-17-producing cells in draining lymph nodes. Importantly, the treatment did not inhibit T-cell division per se. In mice with established experimental autoimmune encephalomyelitis, the numbers of Ly6C(hi) CD115(+) inflammatory monocytes and CD11b(+)CD11c(+) dendritic cells (DCs) were reduced in spleen, but not in bone marrow or draining lymph nodes of treated mice. Inflammatory monocyte-derived DCs and CD4(+) T cells were also reduced in the brain. In contrast, there was no decrease in DC subsets previously shown to be critical for effector CD4(+) T-cell development in lymph nodes. Taken together, these data indicate that preventive treatment with paquinimod ameliorates experimental autoimmune encephalomyelitis by reducing effector T-cell priming and, on prolonged treatment, displays a selective effect by decreasing distinct subpopulations of splenic CD11b(+) myeloid cells.}},
author = {{Helmersson, Sofia and Sundstedt, Anette and Deronic, Adnan and Leanderson, Tomas and Ivars, Fredrik}},
issn = {{1525-2191}},
language = {{eng}},
number = {{5}},
pages = {{1671--1680}},
publisher = {{American Society for Investigative Pathology}},
series = {{American Journal of Pathology}},
title = {{Amelioration of Experimental Autoimmune Encephalomyelitis by the Quinoline-3-Carboxamide Paquinimod (ABR-215757): Reduced Priming of Proinflammatory Effector CD4(+) T Cells.}},
url = {{http://dx.doi.org/10.1016/j.ajpath.2013.01.032}},
doi = {{10.1016/j.ajpath.2013.01.032}},
volume = {{182}},
year = {{2013}},
}