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Eosinophils are classically known as proinflammatory cells, as they are equipped with a variety of preformed cytotoxic mediators and have been shown to definitively contribute to asthma. The connection between eosinophils and asthma development has led to a new class of asthma therapeutics based on blocking eosinophils with humanized antibodies that neutralize IL-5, a potent eosinophil growth, activation, and survival factor. Yet, recent studies have led to an increasing appreciation that eosinophils have a variety of homeostatic functions, including immunomodulation. In this issue of the JCI, Mesnil et al. identify a notable population of lung-resident eosinophils and demonstrate that, compared with traditional eosinophils, these cells have distinct characteristics, including nuclear structure, surface markers, IL-5 independence, and immunoregulatory function that is capable of polarizing adaptive immune responses, at least in vitro. Thus, these results reinforce a key homeostatic role for this enigmatic cell population, particularly in residing and regulating immunity in the lung., Eosinophils: traditionally proinflammatory Eosinophils are traditionally viewed as proinflammatory cells, as they are equipped with a variety of preformed cytotoxic mediators, including the granule proteins major basic protein (MBP) and [...]

Eosinophilic inflammation is a cornerstone of chronic asthma that often culminates in subepithelial fibrosis with variable airway obstruction. Pulmonary eosinophils (Eos) are a predominant source of TGF-[beta]1, which drives fibroblast proliferation and extracellular matrix deposition. We investigated the regulation of TGF-[beta]1 and show here that the peptidyl-prolyl isomerase (PPIase) Pin1 promoted the stability of TGF-[beta]1 mRNA in human Eos. In addition, Pin1 regulated cytokine production by both in vitro and in vivo activated human Eos. We found that Pin1 interacted with both PKC-[alpha] and protein phosphatase 2A, which together control Pin1 isomerase activity. Pharmacologic blockade of Pin1 in a rat asthma model selectively reduced eosinophilic pulmonary inflammation, TGF-[beta]1 and collagen expression, and airway remodeling. Furthermore, chronically challenged Pin1-/- mice showed reduced peribronchiolar collagen deposition compared with wild-type controls. These data suggest that pharmacologic suppression of Pin1 may be a novel therapeutic option to prevent airway fibrosis in individuals with chronic asthma., Introduction Persistent asthma is characterized by chronic pulmonary inflammation, which often culminates in airway fibrosis. The development of airway disease is referred to as remodeling and includes the deposition of [...]