Cargando…
TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is a ligand for the aryl hydrocarbon receptor (AhR). TCDD is well-characterized to produce immunotoxicity, including suppression of antibody production. Previously we showed that TCDD inhibited myelin oligodendrocyte glycopr...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788515/ https://www.ncbi.nlm.nih.gov/pubmed/35076460 http://dx.doi.org/10.3390/antib11010004 |
_version_ | 1784639583296684032 |
---|---|
author | Nicaise, Ashleigh J. McDonald, Amye Sears, Erin Rushing Sturgis, Trell Kaplan, Barbara L. F. |
author_facet | Nicaise, Ashleigh J. McDonald, Amye Sears, Erin Rushing Sturgis, Trell Kaplan, Barbara L. F. |
author_sort | Nicaise, Ashleigh J. |
collection | PubMed |
description | The environmental contaminant 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is a ligand for the aryl hydrocarbon receptor (AhR). TCDD is well-characterized to produce immunotoxicity, including suppression of antibody production. Previously we showed that TCDD inhibited myelin oligodendrocyte glycoprotein (MOG) peptide-specific IgG and attenuated disease in experimental autoimmune encephalomyelitis (EAE) model in mice. Thus, the purpose of this study was to characterize the effects of TCDD on IgG subclasses in EAE and in vitro and assess effects in B cells derived from various tissues. TCDD modestly suppressed intracellular IgG expression in splenocytes (SPLC), but not bone marrow (BM) or lymph node (LN) cells. To further understand TCDD’s effects on IgG, we utilized LPS and LPS + IL-4 in vitro to stimulate IgG3 and IgG1 production, respectively. TCDD preferentially suppressed IgG1+ cell surface expression, especially in SPLC. However, TCDD was able to suppress IgG1 and IgG3 secretion from SPLC and B cells, but not BM cells. Lastly, we revisited the EAE model and determined that TCDD suppressed MOG-specific IgG1 production. Together these data show that the IgG1 subclass of IgG is a sensitive target of suppression by TCDD. Part of the pathophysiology of EAE involves production of pathogenic antibodies that can recruit cytolytic cells to destroy MOG-expressing cells that comprise myelin, so inhibition of IgG1 likely contributes to TCDD’s EAE disease attenuation. |
format | Online Article Text |
id | pubmed-8788515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87885152022-01-26 TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro Nicaise, Ashleigh J. McDonald, Amye Sears, Erin Rushing Sturgis, Trell Kaplan, Barbara L. F. Antibodies (Basel) Article The environmental contaminant 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is a ligand for the aryl hydrocarbon receptor (AhR). TCDD is well-characterized to produce immunotoxicity, including suppression of antibody production. Previously we showed that TCDD inhibited myelin oligodendrocyte glycoprotein (MOG) peptide-specific IgG and attenuated disease in experimental autoimmune encephalomyelitis (EAE) model in mice. Thus, the purpose of this study was to characterize the effects of TCDD on IgG subclasses in EAE and in vitro and assess effects in B cells derived from various tissues. TCDD modestly suppressed intracellular IgG expression in splenocytes (SPLC), but not bone marrow (BM) or lymph node (LN) cells. To further understand TCDD’s effects on IgG, we utilized LPS and LPS + IL-4 in vitro to stimulate IgG3 and IgG1 production, respectively. TCDD preferentially suppressed IgG1+ cell surface expression, especially in SPLC. However, TCDD was able to suppress IgG1 and IgG3 secretion from SPLC and B cells, but not BM cells. Lastly, we revisited the EAE model and determined that TCDD suppressed MOG-specific IgG1 production. Together these data show that the IgG1 subclass of IgG is a sensitive target of suppression by TCDD. Part of the pathophysiology of EAE involves production of pathogenic antibodies that can recruit cytolytic cells to destroy MOG-expressing cells that comprise myelin, so inhibition of IgG1 likely contributes to TCDD’s EAE disease attenuation. MDPI 2022-01-09 /pmc/articles/PMC8788515/ /pubmed/35076460 http://dx.doi.org/10.3390/antib11010004 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nicaise, Ashleigh J. McDonald, Amye Sears, Erin Rushing Sturgis, Trell Kaplan, Barbara L. F. TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro |
title | TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro |
title_full | TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro |
title_fullStr | TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro |
title_full_unstemmed | TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro |
title_short | TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro |
title_sort | tcdd inhibition of igg1 production in experimental autoimmune encephalomyelitis (eae) and in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788515/ https://www.ncbi.nlm.nih.gov/pubmed/35076460 http://dx.doi.org/10.3390/antib11010004 |
work_keys_str_mv | AT nicaiseashleighj tcddinhibitionofigg1productioninexperimentalautoimmuneencephalomyelitiseaeandinvitro AT mcdonaldamye tcddinhibitionofigg1productioninexperimentalautoimmuneencephalomyelitiseaeandinvitro AT searserinrushing tcddinhibitionofigg1productioninexperimentalautoimmuneencephalomyelitiseaeandinvitro AT sturgistrell tcddinhibitionofigg1productioninexperimentalautoimmuneencephalomyelitiseaeandinvitro AT kaplanbarbaralf tcddinhibitionofigg1productioninexperimentalautoimmuneencephalomyelitiseaeandinvitro |