Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines.

Abstract:

:Mast cells (MCs) are potent inflammatory cells that are distributed throughout mucosal barrier tissues and respond rapidly to pathogenic stimuli. During helminth infections, MCs play an important role as late-stage effectors. However, it is currently unknown whether MCs contribute to the early innate events that determine the priming of adaptive immunity. MC-deficient mouse strains and mice treated with the MC stabilizing agent cromolyn sodium had dramatically reduced Th2 priming and type 2 cytokine production and harbored increased parasite burdens following infection with gastrointestinal helminths (Heligmosomoides polygyrus bakeri and Trichuris muris). In addition, early production of the tissue-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) was significantly diminished in MC-deficient mice and resulted in decreased numbers of infection-elicited IL-25-dependent (Lin(-)CD45(-))CD34(+)Sca-1(+) progenitors, which produced type 2 cytokines and could be differentiated into mast cells ex vivo. Finally, repair of MC deficiency increased production of IL-25, IL-33, and TSLP, restored progenitor cell numbers and Th2 priming, and reduced parasite burden. Our data reveal an innate IgE-independent role for MCs in orchestrating type 2 immune responses via the regulation of IL-25, IL-33, and TSLP.

authors

Hepworth MR,Daniłowicz-Luebert E,Rausch S,Metz M,Klotz C,Maurer M,Hartmann S

doi

10.1073/pnas.1112268109

subject

Has Abstract

pub_date

2012-04-24 00:00:00

pages

6644-9

issue

17

eissn

0027-8424

issn

1091-6490

pii

1112268109

journal_volume

109

pub_type

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