Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness

Journal of Leukocyte Biology

Antoine Neel, –⁴  Michèle Heslan¹  Cécile Braudeau,  and³  Régis Josien, ²  Caroline Hémont, ² 

[1] INSERM UMR064, Nantes, France;  Institut de Transplantation“Urologie“Néphrologie,;INSERM UMR064, Nantes, France;  Institut de Transplantation“Urologie“Néphrologie, Laboratoire d'Immunologie, and Université de Nantes, Faculté de Médecine, Nantes, France;INSERM UMR064, Nantes, France;  Institut de Transplantation“Urologie“Néphrologie, Laboratoire d'Immunologie,INSERM UMR064, Nantes, France;  Institut de Transplantation“Urologie“Néphrologie, –Service de Médecine Interne, CHU Nantes, Nantes, France;

关键词: dendritic cells;    CD141;    Toll-like receptors;    cytokines;   

DOI  :  10.1189/jlb.0912452

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Human blood DCs encompass pDCs and two subsets of mDCs: CD1c+ mDCs and CD141+ mDCs. The rare CD141+ DC population is thought to be the equivalent of mouse CD8α+ cDCs that play a significant role in antigen cross-presentation. Here, we analyzed by Q-PCR TLR1–10 expression in blood DC subsets. Whereas CD1c+ DCs express all TLR except TLR9, CD141+ DCs present a more restricted pattern with high expression of TLR3 and -10, expression of TLR1,-2, -6, and -8, and lack of TLR4, -5, -7, and -9. The in vitro analysis of isolated mDC subset reponsiveness to an extensive panel of TLR ligands confirmed these results, with CD141+ DCs responding only to TLR1/2, -3, and -7/8. The cytokine/chemokine production profile of isolated CD141+ DCs was also more restricted, as they produced mainly proinflammatory cytokines but no IL-12 and to a lower level, in comparison with CD1c+ DCs, except for CXCL10, CCL5, and IFN-β. In contrast, with the use of a whole blood assay, we found that CD141+ DCs produce IL-12 in response to TLR1/2, -3, and more surprisingly, -9. Finally, both mDC subsets are potent inducers of Th1 response, particularly after TLR3 triggering. Taken together, these data confirmed functional differences between blood mDC subsets. The major response of CD141+ mDCs to TLR3 ligand and their cytokine production pattern suggest a role for these cells in antiviral immunity.

【 授权许可】

Unknown