期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 216, 期 7, 页码 1561-1581出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20181994
关键词
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资金
- Institut National de la Sante et de la Recherche Medicale
- Agence Nationale de la Recherche [ANR-10-LABX-0043, ANR-CHIN-0002, ANR-10-IDEX-0001-02 PSL, HI-FISH ANR-14-CE10-0018-01]
- Institut Curie (CIC IGR-Curie) [1428]
- European Research Council [340046 DCBIOX]
- Fondation ARC pour la recherche contre le cancer
- Universite Paris Descartes
- Ligue contre le Cancer
- Equipex [ANR-10-EQPX-03]
- France Genomique Consortium [ANR-10-INBS-09-08]
- Canceropole Ile-de-France
- SESAME program from Region Ile-de-France
- Site de Recherche Integree sur le Cancer-Curie program (Site de Recherche Integree sur le Cancer grant) [INCa-DGOS-4654]
- La Ligue Nationale contre le Cancer [EL2014.LNCC/SA]
CD4(+) T follicular helper (Tfh) cells are essential for inducing efficient humoral responses. T helper polarization is classically orientated by dendritic cells (DCs), which are composed of several subpopulations with distinct functions. Whether human DC subsets display functional specialization for Tfh polarization remains unclear. Here we find that tonsil cDC2 and CD14(+) macrophages are the best inducers of Tfh polarization. This ability is intrinsic to the cDC2 lineage but tissue dependent for macrophages. We further show that human Tfh cells comprise two effector states producing either IL-21 or CXCL13. Distinct mechanisms drive the production of Tfh effector molecules, involving IL-12p70 for IL-21 and activin A and TGF beta for CXCL13. Finally, using imaging mass cytometry, we find that tonsil CD14(+) macrophages localize in situ in the B cell follicles, where they can interact with Tfh cells. Our results indicate that human lymphoid organ cDC2 and macrophages play complementary roles in the induction of Tfh responses.
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