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CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells.

Henri S, Poulin LF, Tamoutounour S, Ardouin L, Guilliams M, de Bovis B, Devilard E, Viret C, Azukizawa H, Kissenpfennig A, Malissen B - J. Exp. Med. (2009)

Bottom Line: We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E alpha.Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs.Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.

ABSTRACT
Recent studies have challenged the view that Langerhans cells (LCs) constitute the exclusive antigen-presenting cells of the skin and suggest that the dermal dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track and ablate DCs expressing langerin (CD207), we discovered that the dermis contains five distinct DC subsets and identified their migratory counterparts in draining lymph nodes. Based on this refined classification, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E alpha. Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs. Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

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Draining CLNs contain five skin-derived DC subsets. Flow cytometry analysis of the skin-derived migratory DCs (MHCIIhigh CD11cinter-to-high) present in CLNs from C57BL/6 (B6) mice and B6 (CD45.1)→B6 (CD45.2) BM chimeras. MHCIIhigh CD11cinter-to-high DCs were analyzed for the expression of CD207 versus CD11b and CD103 expression determined on each of the specified DC subsets. (A) A single CD207+ CD11b−/low DC cluster is present in the CLNs of B6 mice. Unlike DDCs, LCs are radio resistant, and this permits the use of B6 (CD45.1)→B6 (CD45.2) chimeras to split the single CD207+ CD11b−/low DC cluster into host-derived mLCs and into CD103+ and CD103− donor-derived mDDCs. Two additional mDDC subsets with a CD207+ CD11b− and CD207− CD11b+ phenotype can be identified in both C57BL/6 mice and B6 (CD45.1)→B6 (CD45.2) chimeras. (B) Expression of CD103 among the DC subsets found in the dermis of B6 (CD45.1)→B6 (CD45.2) BM chimeras. The percentages of cells found in each of the specified gates are indicated. Data shown are representative of at least 12 chimeric mice corresponding to six independent experiments.
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fig3: Draining CLNs contain five skin-derived DC subsets. Flow cytometry analysis of the skin-derived migratory DCs (MHCIIhigh CD11cinter-to-high) present in CLNs from C57BL/6 (B6) mice and B6 (CD45.1)→B6 (CD45.2) BM chimeras. MHCIIhigh CD11cinter-to-high DCs were analyzed for the expression of CD207 versus CD11b and CD103 expression determined on each of the specified DC subsets. (A) A single CD207+ CD11b−/low DC cluster is present in the CLNs of B6 mice. Unlike DDCs, LCs are radio resistant, and this permits the use of B6 (CD45.1)→B6 (CD45.2) chimeras to split the single CD207+ CD11b−/low DC cluster into host-derived mLCs and into CD103+ and CD103− donor-derived mDDCs. Two additional mDDC subsets with a CD207+ CD11b− and CD207− CD11b+ phenotype can be identified in both C57BL/6 mice and B6 (CD45.1)→B6 (CD45.2) chimeras. (B) Expression of CD103 among the DC subsets found in the dermis of B6 (CD45.1)→B6 (CD45.2) BM chimeras. The percentages of cells found in each of the specified gates are indicated. Data shown are representative of at least 12 chimeric mice corresponding to six independent experiments.

Mentions: Expression of EpCAM, CD24, F4/80, and SIRPα on the five skin DC subsets before and after their migration to CLNs. DC subsets were prepared as specified in Figs. 1 and 3 from dermis and CLNs from B6 (CD45.1)→B6 (CD45.2) BM chimeras and analyzed for the expression of EpCAM, CD24, F4/80, and SIRPα. Isotype control staining is shown by the shaded histograms. In steady-state skin, LCs and CD207− CD11b+ DDCs were homogeneously F4/80+. CD207− CD11b− DDCs showed a heterogeneous pattern of F4/80 expression, whereas both subsets of CD207+ DDCs were F4/80−. Upon migration to the CLNs, F4/80 expression was down-regulated on mLCs and CD207− mDDCs. If we except mLCs that showed a slight decrease in Sirpα levels, Sirpα expression was up-regulated or induced on all the remaining skin-derived migratory DC subsets. Data shown are representative of at least six chimeric mice corresponding to three independent experiments.


CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells.

Henri S, Poulin LF, Tamoutounour S, Ardouin L, Guilliams M, de Bovis B, Devilard E, Viret C, Azukizawa H, Kissenpfennig A, Malissen B - J. Exp. Med. (2009)

Draining CLNs contain five skin-derived DC subsets. Flow cytometry analysis of the skin-derived migratory DCs (MHCIIhigh CD11cinter-to-high) present in CLNs from C57BL/6 (B6) mice and B6 (CD45.1)→B6 (CD45.2) BM chimeras. MHCIIhigh CD11cinter-to-high DCs were analyzed for the expression of CD207 versus CD11b and CD103 expression determined on each of the specified DC subsets. (A) A single CD207+ CD11b−/low DC cluster is present in the CLNs of B6 mice. Unlike DDCs, LCs are radio resistant, and this permits the use of B6 (CD45.1)→B6 (CD45.2) chimeras to split the single CD207+ CD11b−/low DC cluster into host-derived mLCs and into CD103+ and CD103− donor-derived mDDCs. Two additional mDDC subsets with a CD207+ CD11b− and CD207− CD11b+ phenotype can be identified in both C57BL/6 mice and B6 (CD45.1)→B6 (CD45.2) chimeras. (B) Expression of CD103 among the DC subsets found in the dermis of B6 (CD45.1)→B6 (CD45.2) BM chimeras. The percentages of cells found in each of the specified gates are indicated. Data shown are representative of at least 12 chimeric mice corresponding to six independent experiments.
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Related In: Results  -  Collection

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fig3: Draining CLNs contain five skin-derived DC subsets. Flow cytometry analysis of the skin-derived migratory DCs (MHCIIhigh CD11cinter-to-high) present in CLNs from C57BL/6 (B6) mice and B6 (CD45.1)→B6 (CD45.2) BM chimeras. MHCIIhigh CD11cinter-to-high DCs were analyzed for the expression of CD207 versus CD11b and CD103 expression determined on each of the specified DC subsets. (A) A single CD207+ CD11b−/low DC cluster is present in the CLNs of B6 mice. Unlike DDCs, LCs are radio resistant, and this permits the use of B6 (CD45.1)→B6 (CD45.2) chimeras to split the single CD207+ CD11b−/low DC cluster into host-derived mLCs and into CD103+ and CD103− donor-derived mDDCs. Two additional mDDC subsets with a CD207+ CD11b− and CD207− CD11b+ phenotype can be identified in both C57BL/6 mice and B6 (CD45.1)→B6 (CD45.2) chimeras. (B) Expression of CD103 among the DC subsets found in the dermis of B6 (CD45.1)→B6 (CD45.2) BM chimeras. The percentages of cells found in each of the specified gates are indicated. Data shown are representative of at least 12 chimeric mice corresponding to six independent experiments.
Mentions: Expression of EpCAM, CD24, F4/80, and SIRPα on the five skin DC subsets before and after their migration to CLNs. DC subsets were prepared as specified in Figs. 1 and 3 from dermis and CLNs from B6 (CD45.1)→B6 (CD45.2) BM chimeras and analyzed for the expression of EpCAM, CD24, F4/80, and SIRPα. Isotype control staining is shown by the shaded histograms. In steady-state skin, LCs and CD207− CD11b+ DDCs were homogeneously F4/80+. CD207− CD11b− DDCs showed a heterogeneous pattern of F4/80 expression, whereas both subsets of CD207+ DDCs were F4/80−. Upon migration to the CLNs, F4/80 expression was down-regulated on mLCs and CD207− mDDCs. If we except mLCs that showed a slight decrease in Sirpα levels, Sirpα expression was up-regulated or induced on all the remaining skin-derived migratory DC subsets. Data shown are representative of at least six chimeric mice corresponding to three independent experiments.

Bottom Line: We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E alpha.Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs.Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.

ABSTRACT
Recent studies have challenged the view that Langerhans cells (LCs) constitute the exclusive antigen-presenting cells of the skin and suggest that the dermal dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track and ablate DCs expressing langerin (CD207), we discovered that the dermis contains five distinct DC subsets and identified their migratory counterparts in draining lymph nodes. Based on this refined classification, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E alpha. Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs. Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

Show MeSH
Related in: MedlinePlus