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Migratory CD11b+ conventional dendritic cells induce T follicular helper cell-dependent antibody responses.

Artikel i vetenskaplig tidskrift
Författare Jayendra Kumar Krishnaswamy
Uthaman Gowthaman
Biyan Zhang
Johan Mattsson
Louis Szeponik
Dong Liu
Renee Wu
Theresa White
Samuele Calabro
Lan Xu
Magalie A Collet
Marina Yurieva
Samuel Alsén
Per Fogelstrand
Anne Walter
William R Heath
Scott N Mueller
Ulf Yrlid
Adam Williams
Stephanie C Eisenbarth
Publicerad i Science immunology
Volym 2
Nummer/häfte 18
ISSN 2470-9468
Publiceringsår 2017
Publicerad vid Wallenberglaboratoriet
Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Språk en
Länkar dx.doi.org/10.1126/sciimmunol.aam91...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Immunbiologi

Sammanfattning

T follicular helper (Tfh) cells are a subset of CD4+ T cells that promote antibody production during vaccination. Conventional dendritic cells (cDCs) efficiently prime Tfh cells; however, conclusions regarding which cDC instructs Tfh cell differentiation have differed between recent studies. We found that these discrepancies might exist because of the unusual sites used for immunization in murine models, which differentially bias which DC subsets access antigen. We used intranasal immunization as a physiologically relevant route of exposure that delivers antigen to all tissue DC subsets. Using a combination of mice in which the function of individual DC subsets is impaired and different antigen formulations, we determined that CD11b+ migratory type 2 cDCs (cDC2s) are necessary and sufficient for Tfh induction. DC-specific deletion of the guanine nucleotide exchange factor DOCK8 resulted in an isolated loss of CD11b+ cDC2, but not CD103+ cDC1, migration to lung-draining lymph nodes. Impaired cDC2 migration or development in DC-specific Dock8 or Irf4 knockout mice, respectively, led to reduced Tfh cell priming, whereas loss of CD103+ cDC1s in Batf3-/- mice did not. Loss of cDC2-dependent Tfh cell priming impaired antibody-mediated protection from live influenza virus challenge. We show that migratory cDC2s uniquely carry antigen into the subanatomic regions of the lymph node where Tfh cell priming occurs-the T-B border. This work identifies the DC subset responsible for Tfh cell-dependent antibody responses, particularly when antigen dose is limiting or is encountered at a mucosal site, which could ultimately inform the formulation and delivery of vaccines.

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