New perspectives on the initiation of allergic immune responses at barrier sites
M Noti - Current Opinion in Immunology, 2018 - Elsevier
Current Opinion in Immunology, 2018•Elsevier
Highlights•Epithelial cells act as primary sentinels of allergens and initiate type-2 immune
responses by secretion of TSLP, IL-33, IL-25 and GM-CSF.•Tuft cell-derived IL-25 can kick-
start type-2 immune responses by activating IL-13 production in ILC2s.•In response to
allergens, mucosal neurons can release neuromedin U to activate ILC2s.•Tezepelumab, a
monoclonal antibody that blocks TSLP, shows efficacy in the management of persistent
uncontrolled asthma.Although allergies exert a devastating global impact and often lack …
responses by secretion of TSLP, IL-33, IL-25 and GM-CSF.•Tuft cell-derived IL-25 can kick-
start type-2 immune responses by activating IL-13 production in ILC2s.•In response to
allergens, mucosal neurons can release neuromedin U to activate ILC2s.•Tezepelumab, a
monoclonal antibody that blocks TSLP, shows efficacy in the management of persistent
uncontrolled asthma.Although allergies exert a devastating global impact and often lack …
Highlights
- Epithelial cells act as primary sentinels of allergens and initiate type-2 immune responses by secretion of TSLP, IL-33, IL-25 and GM-CSF.
- Tuft cell-derived IL-25 can kick-start type-2 immune responses by activating IL-13 production in ILC2s.
- In response to allergens, mucosal neurons can release neuromedin U to activate ILC2s.
- Tezepelumab, a monoclonal antibody that blocks TSLP, shows efficacy in the management of persistent uncontrolled asthma.
Although allergies exert a devastating global impact and often lack effective treatment strategies, our knowledge on the mechanisms that initiate and propagate type-2 immune responses remain enigmatic. Recent advances have highlighted additional roles for epithelial cells (eg tuft cells) and sensory neurons as initiators and amplifiers of type-2 immune responses. In response to protease activity of allergens, Toll-like receptor stimulation or cellular damage, these type-2 sentinels can release cytokines, alarmins or neuropeptides capable of (i) activating and expanding innate immune cells,(ii) polarizing T helper type-2 cells and (iii) promoting allergic inflammation. Overexpression of these type-2 immune mediators has been associated with allergic disorders and together with their disease promoting role in experimental model systems have paved the way for the generation of new biologics. The aim of this review is to provide a concise view on recent developments in the field and to discuss these findings in the context of allergic inflammation.
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