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CD34-derived human Langerhans cells stimulate a T helper type 2 response independently of extracellular-signal-regulated kinase phosphorylation.
Immunology. 2010 Oct; 131(2):210-9.I

Abstract

Dendritic cell (DC) subsets can mediate diverse responses, but little is known about the Toll-like receptor (TLR) signalling pathways in different human DC subsets. Despite expressing many TLRs in common, we found that in vitro-derived Langerhans cells (LCs) and monocyte-derived DCs (moDCs) undergo differential signalling events following TLR stimulation. TLR-stimulated LCs did not secrete interleukin (IL)-12p70 and thus induced a T helper type 2 (Th2)-biased response. moDCs secrete high levels of IL-12p70 and induce a Th1 response. Stimulation of moDCs through TLR2 or TLR7/8 was able to induce phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular-signal-regulated kinase (ERK). However, phosphorylated ERK was not induced in TLR-stimulated LCs, suggesting an ERK-independent method of Th2 cell induction. Inhibition of p38 MAPK suppressed moDC maturation, but was much less effective at inhibiting LC maturation. Phosphatidylinositol-3 kinase (PI3K) was also found to play a greater role in moDC survival compared with the LCs. Polymerase chain reaction (PCR) arrays to compare the expression of signalling molecules in LCs and moDCs identified differences in TLR recognition molecules and cytokine response genes, suggesting that differential functional responses are probably mediated at the post-transcriptional level. Thus we have described differences in LC and moDC responses to TLR stimulation, and have identified key differences in ERK phosphorylation and the involvement of MAPK and PI3K.

Authors+Show Affiliations

Department of Immunology, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20465567

Citation

Duraisingham, Sai S., et al. "CD34-derived Human Langerhans Cells Stimulate a T Helper Type 2 Response Independently of Extracellular-signal-regulated Kinase Phosphorylation." Immunology, vol. 131, no. 2, 2010, pp. 210-9.
Duraisingham SS, Hornig J, Gotch F, et al. CD34-derived human Langerhans cells stimulate a T helper type 2 response independently of extracellular-signal-regulated kinase phosphorylation. Immunology. 2010;131(2):210-9.
Duraisingham, S. S., Hornig, J., Gotch, F., & Patterson, S. (2010). CD34-derived human Langerhans cells stimulate a T helper type 2 response independently of extracellular-signal-regulated kinase phosphorylation. Immunology, 131(2), 210-9. https://doi.org/10.1111/j.1365-2567.2010.03295.x
Duraisingham SS, et al. CD34-derived Human Langerhans Cells Stimulate a T Helper Type 2 Response Independently of Extracellular-signal-regulated Kinase Phosphorylation. Immunology. 2010;131(2):210-9. PubMed PMID: 20465567.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD34-derived human Langerhans cells stimulate a T helper type 2 response independently of extracellular-signal-regulated kinase phosphorylation. AU - Duraisingham,Sai S, AU - Hornig,Julia, AU - Gotch,Frances, AU - Patterson,Steven, PY - 2010/5/15/entrez PY - 2010/5/15/pubmed PY - 2011/1/11/medline SP - 210 EP - 9 JF - Immunology JO - Immunology VL - 131 IS - 2 N2 - Dendritic cell (DC) subsets can mediate diverse responses, but little is known about the Toll-like receptor (TLR) signalling pathways in different human DC subsets. Despite expressing many TLRs in common, we found that in vitro-derived Langerhans cells (LCs) and monocyte-derived DCs (moDCs) undergo differential signalling events following TLR stimulation. TLR-stimulated LCs did not secrete interleukin (IL)-12p70 and thus induced a T helper type 2 (Th2)-biased response. moDCs secrete high levels of IL-12p70 and induce a Th1 response. Stimulation of moDCs through TLR2 or TLR7/8 was able to induce phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular-signal-regulated kinase (ERK). However, phosphorylated ERK was not induced in TLR-stimulated LCs, suggesting an ERK-independent method of Th2 cell induction. Inhibition of p38 MAPK suppressed moDC maturation, but was much less effective at inhibiting LC maturation. Phosphatidylinositol-3 kinase (PI3K) was also found to play a greater role in moDC survival compared with the LCs. Polymerase chain reaction (PCR) arrays to compare the expression of signalling molecules in LCs and moDCs identified differences in TLR recognition molecules and cytokine response genes, suggesting that differential functional responses are probably mediated at the post-transcriptional level. Thus we have described differences in LC and moDC responses to TLR stimulation, and have identified key differences in ERK phosphorylation and the involvement of MAPK and PI3K. SN - 1365-2567 UR - https://www.unboundmedicine.com/medline/citation/20465567/CD34_derived_human_Langerhans_cells_stimulate_a_T_helper_type_2_response_independently_of_extracellular_signal_regulated_kinase_phosphorylation_ DB - PRIME DP - Unbound Medicine ER -