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Selective depletion of splenic CD4 dendritic cells in mice treated with immunomodulatory quinoline-3-carboxamide ABR-215757.

Stenström, Martin LU ; Anderson, Per LU ; Eroukhmanoff, Lena LU ; Leanderson, Tomas LU and Ivars, Fredrik LU (2010) In International Immunopharmacology May 4. p.837-842
Abstract
The quinoline-3-carboxamide ABR-215757 (5757) is in clinical development for the treatment of human SLE and has shown efficacy in several mouse models of T cell-mediated inflammatory autoimmune disease. The goal of this study was to determine the impact of 5757 on steady state immune cells. We show that the number of splenic CD4 dendritic cells (DCs) was reduced in 5757-treated mice, while there was no effect on other splenic DC populations, on DCs in lymph nodes or on lymphocytes. This reduction was fully reversible and the kinetics of CD4 DC loss during exposure and recovery after withdrawal of treatment were identical. The loss of CD4 DCs was neither caused by reduced proliferation nor by increased apoptosis. CD4 DCs reside in the... (More)
The quinoline-3-carboxamide ABR-215757 (5757) is in clinical development for the treatment of human SLE and has shown efficacy in several mouse models of T cell-mediated inflammatory autoimmune disease. The goal of this study was to determine the impact of 5757 on steady state immune cells. We show that the number of splenic CD4 dendritic cells (DCs) was reduced in 5757-treated mice, while there was no effect on other splenic DC populations, on DCs in lymph nodes or on lymphocytes. This reduction was fully reversible and the kinetics of CD4 DC loss during exposure and recovery after withdrawal of treatment were identical. The loss of CD4 DCs was neither caused by reduced proliferation nor by increased apoptosis. CD4 DCs reside in the splenic marginal zone, but the loss of these cells did not influence other cell populations at this site. The similar kinetics of the decay and repopulation of the splenic CD4 DC compartment suggests that the reduced number of CD4 DC in 5757 treated mice may be a result of blockade of CD4 DC precursor development in the spleen and not of toxicity. Alternatively, induced emigration of CD4 DC to the periphery, or an interference with adherence of these cells in the spleen marginal zone, may also explain our data. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Immunopharmacology
volume
May 4
pages
837 - 842
publisher
Elsevier
external identifiers
  • wos:000280888400002
  • pmid:20423734
  • scopus:77954958927
  • pmid:20423734
ISSN
1878-1705
DOI
10.1016/j.intimp.2010.04.011
language
English
LU publication?
yes
id
a015bf67-5012-4cd9-bea9-43acb15bbda7 (old id 1594744)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20423734?dopt=Abstract
date added to LUP
2016-04-04 08:45:07
date last changed
2022-02-20 22:12:28
@article{a015bf67-5012-4cd9-bea9-43acb15bbda7,
  abstract     = {{The quinoline-3-carboxamide ABR-215757 (5757) is in clinical development for the treatment of human SLE and has shown efficacy in several mouse models of T cell-mediated inflammatory autoimmune disease. The goal of this study was to determine the impact of 5757 on steady state immune cells. We show that the number of splenic CD4 dendritic cells (DCs) was reduced in 5757-treated mice, while there was no effect on other splenic DC populations, on DCs in lymph nodes or on lymphocytes. This reduction was fully reversible and the kinetics of CD4 DC loss during exposure and recovery after withdrawal of treatment were identical. The loss of CD4 DCs was neither caused by reduced proliferation nor by increased apoptosis. CD4 DCs reside in the splenic marginal zone, but the loss of these cells did not influence other cell populations at this site. The similar kinetics of the decay and repopulation of the splenic CD4 DC compartment suggests that the reduced number of CD4 DC in 5757 treated mice may be a result of blockade of CD4 DC precursor development in the spleen and not of toxicity. Alternatively, induced emigration of CD4 DC to the periphery, or an interference with adherence of these cells in the spleen marginal zone, may also explain our data.}},
  author       = {{Stenström, Martin and Anderson, Per and Eroukhmanoff, Lena and Leanderson, Tomas and Ivars, Fredrik}},
  issn         = {{1878-1705}},
  language     = {{eng}},
  pages        = {{837--842}},
  publisher    = {{Elsevier}},
  series       = {{International Immunopharmacology}},
  title        = {{Selective depletion of splenic CD4 dendritic cells in mice treated with immunomodulatory quinoline-3-carboxamide ABR-215757.}},
  url          = {{https://lup.lub.lu.se/search/files/5195130/1665752.doc}},
  doi          = {{10.1016/j.intimp.2010.04.011}},
  volume       = {{May 4}},
  year         = {{2010}},
}