Human lymphoid organ cDC2 and macrophages play complementary roles in T follicular helper responses

被引：56

作者：

Durand, Melanie ^{[1
,2
]}

Walter, Thomas ^{[3
,4
]}

Pirnay, Tiphene ^{[1
]}

Naessens, Thomas ^{[5
]}

Gueguen, Paul ^{[1
,2
]}

Goudot, Christel ^{[1
]}

Lameiras, Sonia ^{[6
]}

Chang, Qing ^{[7
]}

Talaei, Nafiseh ^{[7
]}

Ornatsky, Olga ^{[7
]}

Vassilevskaia, Tatiana ^{[7
]}

Baulande, Sylvain ^{[6
]}

Amigorena, Sebastian ^{[1
]}

Segura, Elodie ^{[1
]}

机构：

[1] Paris Sci & Lettres Res Univ, Inst Curie, INSERM, U932, Paris, France

[2] Univ Paris 05, Paris, France

[3] Paris Sci & Lettres Res Univ, Mines ParisTech, Ctr Computat Biol, Paris, France

[4] Paris Sci & Lettres Res Univ, Inst Curie, INSERM, U900, Paris, France

[5] AstraZeneca, Innovat Med & Early Dev Biotech Unit, Target & Translat Sci Resp Inflammat & Autoimmun, Gothenburg, Sweden

[6] Paris Sci & Lettres Res Univ, Inst Curie, Next Generat Sequencing Platform, Paris, France

[7] Fluidigm Canada Inc, Markham, ON, Canada

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2019年 / 216卷 / 07期

基金：

欧洲研究理事会;

关键词：

DENDRITIC CELLS INDUCE; DIFFERENTIATION; SUBSETS; ANTIGEN; EXPRESSION; RESIDENT; PROMOTE; PROGRAM; CLEC9A; BLOOD;

D O I：

10.1084/jem.20181994

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1561 / 1581

页数：21

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