+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Consequences of AhR activation in steady-state dendritic cells

, : Consequences of AhR activation in steady-state dendritic cells. Toxicological Sciences 119(2): 293-307

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototypical aryl hydrocarbon receptor (AhR) ligand and a potent immunotoxicant. However, the mechanisms underlying TCDD-induced immunomodulation remain to be defined. Dendritic cells are professional antigen-presenting cells that constitutively express the AhR and are sensitive to TCDD-induced AhR activation. We hypothesized that AhR activation alters the differentiation and function of steady-state bone marrow-derived dendritic cells (BMDCs). To test this hypothesis, steady-state BMDCs from C57BL/6 mice were grown in the presence of TCDD or vehicle. TCDD-treated steady-state BMDCs (TCDD-BMDCs) displayed decreased expression of CD11c and CD11a, whereas increasing the frequency of major histocompatibility complex class II, CD86, CD80, and CD54. Similar phenotypic alterations were observed with the AhR ligands 6-formylindolo[3,2-b]carbazole and 2-(1H-indole-3'-carbonyl)-thiazole-4-carboxylic acid (ITE). TCDD-BMDCs from AhR(-/-) mice were refractory to TCDD-induced surface marker alterations, whereas TCDD-BMDCs from AhR(dbd/dbd) mice displayed similar phenotypic alterations as AhR(+/+) TCDD-BMDCs. Following lipopolysaccharide (LPS), cytosine-phosphate-guanine (CpG), or Imiquimod stimulation, TCDD-BMDCs secreted less interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-10, and IL-12. TCDD also altered NF-κB family member-binding activity in unstimulated and LPS- or CpG-stimulated steady-state BMDCs. The internalization of the soluble antigens, ovalbumin, and acetylated low-density lipoprotein was decreased, whereas internalization of latex beads was increased in TCDD-BMDCs when compared with vehicle-BMDCs. TCDD-BMDCs displayed increased messenger RNA expression of the regulatory gene IDO2 and following LPS stimulation upregulated IDO1, IDO2, TGFβ1, and TGFβ3 gene expression. Additionally, TCDD-BMDCs increased the generation of CD4(+) CD25(+) FoxP3(+) Tregs in vitro in an IDO-dependent fashion. However, TCDD-treated BMDCs did not alter antigen-specific T-cell activation in vivo. Overall, TCDD-induced AhR activation alters the differentiation, activation, innate, and immunoregulatory function but not the T cell-activating capacity of steady-state BMDCs.


PMID: 21097750

DOI: 10.1093/toxsci/kfq354

Other references

Leinonen H., 1980: Peripheral blood flow in chronic ergotism. Muscle blood flow (MBF) was determined in 11 patients on chronic overdoses of ergotamine tartrate [a drug used in the treatment of migraine] and in 12 controls, using the local 133Xe clearance method. The difference in MBF between the groups was i...

Salinas, L.; Arana, C.; Suni, M., 2007: El nectar de especies de Puya como recurso para picaflores Altoandinos de Ancash, Peru. In the high Andean region of Ancash the greatest diversity of flowers ornithophilous is in shrublands, in contrast to rocky areas and grasslands, in those that we find stands of bromelias of the genera Puya whose nectar could constitute an import...

Roychoudhury, S.; Makin, K.; Twinem, T.; Leunk, R.; Hsu, M.Chu., 2016: In Vitro Resistance Development to Nemonoxacin in Streptococcus pneumoniae: A Unique Profile for a Novel Nonfluorinated Quinolone. NlmCategory="UNASSIGNED">Selection of resistant strains in Streptococcus pneumoniae was studied in vitro with nemonoxacin, a novel nonfluorinated quinolone (NFQ), in comparison with quinolone benchmarks, ciprofloxacin, garenoxacin, an...

Camara-Besa, S.F.; Bataclan, M., 1954: The sodium and potassium content of Philippine foods. 3. Foods of animal origin. For parts 1 and 2 see Absts. 1644, Vol. 24; 1760, Vol. 25. 3. Values obtained with the flame photometer are tabulated on a fresh and dry basis, in mg. per 100 g. edible portion, for 340 items, including 61 meat cuts from cow, pig, carabao, deer, r...

Ortega Fleitas, O.; Camejo Corrales, J.; Otero, M.; Fonseca, M., 1996: Colourants in the manufacture of buffalo milk butter. 1. Utilization of Bixa orellana. The effect of using a fat-soluble extract from Bixa orellana (BFE) on the colour of butter made from buffalo milk was studied in a 3 x 3 factorial design experiment with BFE and fat concentration in cream (FC) as independent variables and colour d...

Bruker, I.E., 1971: Blood volume changes in pulmonary tuberculosis in relation to surgery. Grudnaia Khirurgiia 13(1): 95-96

Ball, B.C.; Smith, K.A., 1991: Gas movement. The following methods are described: (a) determination of diffusion by laboratory and field methods; (b) the determination of mass flow; and (c) the determination of air-filled porosity. The following applications are discussed: (a) soil structure...

Trail, DS., 1981: Predation by Argyrodes (Theridiidae) on solitary and communal spiders. Psyche (Cambridge). 1980 ; 873-4: 349-355

Qiu, J.; Lou, L.G.; Huang, X.Y.; Lou, S.J.; Pei, G.; Chen, Y.Z., 1998: Nongenomic mechanisms of glucocorticoid inhibition of nicotine-induced calcium influx in PC12 cells: involvement of protein kinase C. Nongenomic mechanisms of corticosterone (B) inhibition of nicotine (Nic)-induced calcium influx were investigated in PC12 cells. Corticosterone could rapidly inhibit the Ca2+ influx induced by Nic, and BSA-conjugated B had a similar inhibitory eff...

Rau, P.V.; Rao, R.S.; Sharma, S.; Shah, M.; Ramachandiran; Bansal, R.D., 1988: Concomitant helminthiasis and recurrent upper respiratory tract infection in children of an urban community in Pondicherry. Indian Journal of Public Health 32(1): 39-40