TY - JOUR
T1 - Flt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells
AU - Mollah, Shamim A.
AU - Dobrin, Joseph S.
AU - Feder, Rachel E.
AU - Tse, Sze Wah
AU - Matos, Ines G.
AU - Cheong, Cheolho
AU - Steinman, Ralph M.
AU - Anandasabapathy, Niroshana
N1 - Funding Information:
We are deeply grateful to Ralph M. Steinman for his mentorship, support, and wisdom. We are grateful to Tibor Keler and Celldex therapeutics for use of recombinant Flt3L; Andrew Sikora and Paola Longhi for critical reading of the manuscript; Jim Krueger for mentorship; Judy Adams for assistance with figure graphics, and Klara Velinzon for assistance with flow sorting. N.A. was supported in part by grant UL1TR000043/ KL2TR000151 from the National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, the Dermatology Foundation, the Klarman Family Foundation, and supported by NIH grants AI40045, 81677, and 13013 (to R.M.S) and NIAMS AR063461-01A1 (to N.A.). C.C. is supported by the grant from the Canadian Institutes of Health Resarch (CIHR) and Chercheur-Boursier Junor of Fonds de recherché du Quebec-Santé (FRSQ). S.T. is supported by NIAMS 5T32AR007098-39. We thank the Harvard Neurobiology Department and the Neurobiology Imaging Facility for consultation and instrument availability that supported this work. This facility is supported in part by the Neural Imaging Center as part of an NINDS P30 Core Center grant #NS072030.
Publisher Copyright:
© 2014 The Society for Investigative Dermatology.
PY - 2014
Y1 - 2014
N2 - Skin-derived dendritic cells (DCs) are potent antigen-presenting cells with critical roles in both adaptive immunity and tolerance to self. Skin DCs carry antigens and constitutively migrate to the skin-draining lymph nodes (LNs). In mice, Langerin-CD11b- dermal DCs are a low-frequency, heterogeneous, migratory DC subset that traffics to LNs (Langerin-CD11b- migDCs). Here, we build on the observation that Langerin-CD11b- migDCs are Fms-like tyrosine kinase 3 ligand (Flt3L) dependent and strongly Flt3L responsive, which may relate them to classical DCs. Examination of DC capture of FITC from painted skin, DC isolation from skin explant culture, and from the skin of CCR7 knockout mice, which accumulate migDCs, demonstrate these cells are cutaneous residents. Langerin-CD11b- Flt3L-responsive DCs are largely CD24(+) and CX 3 CR1 low and can be depleted from Zbtb46-DTR mice, suggesting classical DC lineage. Langerin-CD11b- migDCs present antigen with equal efficiency to other DC subsets ex vivo, including classical CD8α cDCs and Langerin+CD103+ dermal DCs. Finally, transcriptome analysis suggests a close relationship with other skin DCs, and a lineage relationship with other classical DCs. This work demonstrates that Langerin- CD11b- dermal DCs, a previously overlooked cell subset, may be an important contributor to the cutaneous immune environment.
AB - Skin-derived dendritic cells (DCs) are potent antigen-presenting cells with critical roles in both adaptive immunity and tolerance to self. Skin DCs carry antigens and constitutively migrate to the skin-draining lymph nodes (LNs). In mice, Langerin-CD11b- dermal DCs are a low-frequency, heterogeneous, migratory DC subset that traffics to LNs (Langerin-CD11b- migDCs). Here, we build on the observation that Langerin-CD11b- migDCs are Fms-like tyrosine kinase 3 ligand (Flt3L) dependent and strongly Flt3L responsive, which may relate them to classical DCs. Examination of DC capture of FITC from painted skin, DC isolation from skin explant culture, and from the skin of CCR7 knockout mice, which accumulate migDCs, demonstrate these cells are cutaneous residents. Langerin-CD11b- Flt3L-responsive DCs are largely CD24(+) and CX 3 CR1 low and can be depleted from Zbtb46-DTR mice, suggesting classical DC lineage. Langerin-CD11b- migDCs present antigen with equal efficiency to other DC subsets ex vivo, including classical CD8α cDCs and Langerin+CD103+ dermal DCs. Finally, transcriptome analysis suggests a close relationship with other skin DCs, and a lineage relationship with other classical DCs. This work demonstrates that Langerin- CD11b- dermal DCs, a previously overlooked cell subset, may be an important contributor to the cutaneous immune environment.
UR - http://www.scopus.com/inward/record.url?scp=84900859178&partnerID=8YFLogxK
U2 - 10.1038/jid.2013.515
DO - 10.1038/jid.2013.515
M3 - Article
C2 - 24288007
AN - SCOPUS:84900859178
SN - 0022-202X
VL - 134
SP - 1265
EP - 1275
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -