Identification of lineage relationships and novel markers of blood and skin human dendritic cells

Andrew N Harman, Chris R Bye, Najla Nasr, Kerrie J Sandgren, Min Kim, Sarah Mercier, Rachel A Botting, Sharon R Lewin, Anthony L Cunningham, Paul Urquhart Cameron

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Abstract

The lineage relationships and fate of human dendritic cells (DCs) have significance for a number of diseases including HIV where both blood and tissue DCs may be infected. We used gene expression profiling of human monocyte and DC subpopulations sorted directly from blood and skin to define the lineage relationships. We also compared these with monocyte-derived DCs (MDDCs) and MUTZ3 Langerhans cells (LCs) to investigate their relevance as model skin DCs. Hierarchical clustering analysis showed that myeloid DCs clustered according to anatomical origin rather than putative lineage. Plasmacytoid DCs formed the most discrete cluster, but ex vivo myeloid cells formed separate clusters of cells both in blood and in skin. Separate and specific DC populations could be determined within skin, and the proportion of CD14+ dermal DCs (DDCs) was reduced and CD1a+ DDCs increased during culture, suggesting conversion to CD1a+-expressing cells in situ. This is consistent with origin of the CD1a+ DDCs from a local precursor rather than directly from circulating blood DCs or monocyte precursors. Consistent with their use as model skin DCs, the in vitro?derived MDDC and MUTZ3 LC populations grouped within the skin DC cluster. MDDCs clustered most closely to CD14+ DDCs; furthermore, common unique patterns of C-type lectin receptor expression were identified between these two cell types. MUTZ3 LCs, however, did not cluster closely with ex vivo?derived LCs. We identified differential expression of novel genes in monocyte and DC subsets including genes related to DC surface receptors (including C-type lectin receptors, TLRs, and galectins).
Original languageEnglish
Pages (from-to)66 - 79
Number of pages14
JournalJournal of Immunology
Volume190
Issue number1
DOIs
Publication statusPublished - 2013

Cite this

Harman, A. N., Bye, C. R., Nasr, N., Sandgren, K. J., Kim, M., Mercier, S., ... Cameron, P. U. (2013). Identification of lineage relationships and novel markers of blood and skin human dendritic cells. Journal of Immunology, 190(1), 66 - 79. https://doi.org/10.4049/jimmunol.1200779
Harman, Andrew N ; Bye, Chris R ; Nasr, Najla ; Sandgren, Kerrie J ; Kim, Min ; Mercier, Sarah ; Botting, Rachel A ; Lewin, Sharon R ; Cunningham, Anthony L ; Cameron, Paul Urquhart. / Identification of lineage relationships and novel markers of blood and skin human dendritic cells. In: Journal of Immunology. 2013 ; Vol. 190, No. 1. pp. 66 - 79.
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Harman, AN, Bye, CR, Nasr, N, Sandgren, KJ, Kim, M, Mercier, S, Botting, RA, Lewin, SR, Cunningham, AL & Cameron, PU 2013, 'Identification of lineage relationships and novel markers of blood and skin human dendritic cells', Journal of Immunology, vol. 190, no. 1, pp. 66 - 79. https://doi.org/10.4049/jimmunol.1200779

Identification of lineage relationships and novel markers of blood and skin human dendritic cells. / Harman, Andrew N; Bye, Chris R; Nasr, Najla; Sandgren, Kerrie J; Kim, Min; Mercier, Sarah; Botting, Rachel A; Lewin, Sharon R; Cunningham, Anthony L; Cameron, Paul Urquhart.

In: Journal of Immunology, Vol. 190, No. 1, 2013, p. 66 - 79.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Harman, Andrew N

AU - Bye, Chris R

AU - Nasr, Najla

AU - Sandgren, Kerrie J

AU - Kim, Min

AU - Mercier, Sarah

AU - Botting, Rachel A

AU - Lewin, Sharon R

AU - Cunningham, Anthony L

AU - Cameron, Paul Urquhart

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AB - The lineage relationships and fate of human dendritic cells (DCs) have significance for a number of diseases including HIV where both blood and tissue DCs may be infected. We used gene expression profiling of human monocyte and DC subpopulations sorted directly from blood and skin to define the lineage relationships. We also compared these with monocyte-derived DCs (MDDCs) and MUTZ3 Langerhans cells (LCs) to investigate their relevance as model skin DCs. Hierarchical clustering analysis showed that myeloid DCs clustered according to anatomical origin rather than putative lineage. Plasmacytoid DCs formed the most discrete cluster, but ex vivo myeloid cells formed separate clusters of cells both in blood and in skin. Separate and specific DC populations could be determined within skin, and the proportion of CD14+ dermal DCs (DDCs) was reduced and CD1a+ DDCs increased during culture, suggesting conversion to CD1a+-expressing cells in situ. This is consistent with origin of the CD1a+ DDCs from a local precursor rather than directly from circulating blood DCs or monocyte precursors. Consistent with their use as model skin DCs, the in vitro?derived MDDC and MUTZ3 LC populations grouped within the skin DC cluster. MDDCs clustered most closely to CD14+ DDCs; furthermore, common unique patterns of C-type lectin receptor expression were identified between these two cell types. MUTZ3 LCs, however, did not cluster closely with ex vivo?derived LCs. We identified differential expression of novel genes in monocyte and DC subsets including genes related to DC surface receptors (including C-type lectin receptors, TLRs, and galectins).

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U2 - 10.4049/jimmunol.1200779

DO - 10.4049/jimmunol.1200779

M3 - Article

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JF - Journal of Immunology

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