title: Skin dendritic cells induce follicular helper T cells and protective humoral immune responses.
abstract: BACKGROUND
  The contribution of individual subsets of dendritic cells (DCs) to generation of adaptive immunity is central to understanding immune homeostasis and protective immune responses.
  
  
  OBJECTIVE
  We sought to define functions for steady-state skin DCs.
  
  
  METHODS
  We present an approach in which we restrict antigen presentation to individual DC subsets in the skin and monitor the effects on endogenous antigen-specific CD4(+) T- and B-cell responses.
  
  
  RESULTS
  Presentation of foreign antigen by Langerhans cells (LC) in the absence of exogenous adjuvant led to a large expansion of T follicular helper (TFH) cells. This was accompanied by B-cell activation, germinal center formation, and protective antibody responses against influenza. The expansion of TFH cells and antibody responses could be elicited by both systemic and topical skin immunization. TFH cell induction was not restricted to LCs and occurred in response to antigen presentation by CD103(+) dermal DCs. CD103(+) DCs, despite inducing similar TFH responses as LCs, were less efficient in induction of germinal center B cells and humoral immune responses. We also found that skin DCs are sufficient to expand CXCR5(+) TFH cells through an IL-6- and IFN-α/β receptor-independent mechanism, but B cells were required for sustained Bcl-6(+) expression.
  
  
  CONCLUSIONS
  These data demonstrate that a major unappreciated function of skin DCs is their promotion of TFH cells and humoral immune responses that potentially represent an efficient approach for vaccination.
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minn.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Tex.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Zurawski
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minn.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Jarrett
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minn.
authors.forename: Brian
authors.initials: B
authors.lastname: Chicoine
authors.affiliation: Department of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, Minn.
authors.forename: Juliet
authors.initials: J
authors.lastname: Crabtree
authors.affiliation: Department of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, Minn.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Peterson
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Tex.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minn.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minn. Electronic address: botond@umn.edu.
authors.forename: Botond Z
authors.initials: BZ
authors.lastname: Igyártó
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D056724:Immunity, Humoral; D007114:Immunization; D007252:Influenza Vaccines / Q000008:administration & dosage; D039001:Integrin alpha Chains / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D012867:Skin / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; C513179:CXCR5 protein, mouse; D007252:Influenza Vaccines; D039001:Integrin alpha Chains; D015850:Interleukin-6; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D017471:Receptors, Interferon; C091367:alpha E integrins
keywords: Steady-state conditions; T follicular helper cells; protective humoral immune responses; skin dendritic cells