Dataset Information

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

ABSTRACT: 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? 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.

SUBMITTER: Durand M

PROVIDER: S-EPMC6605753 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Durand Mélanie M Walter Thomas T Pirnay Tiphène T Naessens Thomas T Gueguen Paul P Goudot Christel C Lameiras Sonia S Chang Qing Q Talaei Nafiseh N Ornatsky Olga O Vassilevskaia Tatiana T Baulande Sylvain S Amigorena Sebastian S Segura Elodie E

The Journal of experimental medicine 20190509 7

CD4<sup>+</sup> 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<sup>+</sup> macrophages are the best inducers of Tfh polarization. This ability is intrinsic to the cDC2 lineage but ...[more]

PMID: 31072818

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Project description:Continued gambling to recover losses--'loss chasing'--is a prominent feature of social and pathological gambling. However, little is known about the neuromodulators that influence this behavior. In three separate experiments, we investigated the role of serotonin activity, D(2)/D(3) receptor activity, and beta-adrenoceptor activity on the loss chasing of age and IQ-matched healthy adults randomized to treatment or an appropriate control/placebo. In Experiment 1, participants consumed amino-acid drinks that did or did not contain the serotonin precursor, tryptophan. In Experiment 2, participants received a single 176 ?g dose of the D(2)/D(3) receptor agonist, pramipexole, or placebo. In Experiment 3, participants received a single 80 mg dose of the beta-adrenoceptor blocker, propranolol, or placebo. Following treatment, participants completed a computerized loss-chasing game. Mood and heart rate were measured at baseline and following treatment. Tryptophan depletion significantly reduced the number of decisions made to chase losses, and the number of consecutive decisions to chase, in the absence of marked changes in mood. By contrast, pramipexole significantly increased the value of losses chased and diminished the value of losses surrendered. Propranolol markedly reduced heart rate, but produced no significant changes in loss-chasing behavior. Loss chasing can be thought of as an aversively motivated escape behavior controlled, in part, by the marginal value of continued gambling relative to the value of already accumulated losses. Serotonin and dopamine appear to play dissociable roles in the tendency of individuals to gamble to recover, or to seek to 'escape' from, previous losses. Serotonergic activity seems to promote the availability of loss chasing as a behavioral option, whereas D(2)/D(3) receptor activity produces complex changes in the value of losses judged worth chasing. Sympathetic arousal, at least as mediated by beta-adrenoceptors, does not play a major role in laboratory-based loss-chasing choices.

Dataset Information

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

Publications

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

Similar Datasets

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