| First Author | Hepworth MR | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 17 | Pages | 6644-9 |
| PubMed ID | 22493240 | Mgi Jnum | J:183844 |
| Mgi Id | MGI:5319422 | Doi | 10.1073/pnas.1112268109 |
| Citation | Hepworth MR, et al. (2012) Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines. Proc Natl Acad Sci U S A 109(17):6644-9 |
| abstractText | 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. |
