Opposing functions of thymic stromal lymphopoietin–responsive basophils and dendritic cells in a mouse model of atopic dermatitis

Schwartz, Christian; Eberle, Joerg U.; Hoyler, Thomas; Diefenbach, Andreas; Lechmann, Matthias; Voehringer, David

doi:10.1016/j.jaci.2016.04.031

Cited by 23 publications

(23 citation statements)

References 17 publications

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“…Anti-TSLP antibodies can block the accumulation of basophils in the skin 25 but also inhibit peripheral TSLP-induced basophilia during Trichinella spiralis infection 26 . Experiments with mixed bone marrow chimeras revealed that basophil accumulation in the MC903-treated ear does not require direct recognition of TSLP by basophils 5 . Basophils were further found to cooperate with fibroblasts to promote the recruitment of eosinophils in a murine model of irritant contact dermatitis 27 .…”

Section: Basophil Functions In Type 2 Immune Responsesmentioning

confidence: 98%

“…Interleukin (IL)-3 is the most potent cytokine to promote basophil proliferation, but high concentrations of thymic stromal lymphopoietin (TSLP) can have similar effects 5 . IL-3 and TSLP-elicited basophils differ in terms of their gene expression profiles and may resemble different states of activation rather than representing stable subpopulations of basophils.…”

Section: Basophil Development and Critical Transcription Factorsmentioning

confidence: 99%

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Recent advances in understanding basophil functions in vivo

Voehringer

2017

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Basophils are mainly known as pro-inflammatory effector cells associated with allergy and helminth infections. Although they were identified over 130 years ago, their in vivo functions are still poorly understood. New insights into basophil development and function have been gained by the development of various transgenic mouse lines and staining techniques to detect and purify these cells from different organs. Several studies over the past few years have identified unexpected functions for basophils, including immunomodulatory properties and interactions with other immune cells. Here, I summarize and discuss the main findings.

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Section: Basophil Functions In Type 2 Immune Responsesmentioning

confidence: 98%

Section: Basophil Development and Critical Transcription Factorsmentioning

confidence: 99%

Recent advances in understanding basophil functions in vivo

Voehringer

2017

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“…It has been reported that TSLP elicits basophilia in mice and skin recruitment could be blocked by anti-TSLP antibody suggesting that TSLP promotes skin inflammation through the activation of basophils ( 74 , 141 ). In a recent study, Voehringer and collaborators have demonstrated in a murine model of AD that skin recruitment of basophils occurred without direct TSLP recognition by basophils ( 142 ). Furthermore, basophils did not promote but rather ameliorated skin inflammation, and this effect was dependent on TSLPR expression on murine basophils.…”

Section: Tslp and Allergic Inflammationmentioning

confidence: 99%

Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer

et al. 2018

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Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine originally isolated from a murine thymic stromal cell line. TSLP exerts its biological effects by binding to a high-affinity heteromeric complex composed of thymic stromal lymphopoietin receptor chain and IL-7Rα. TSLP is primarily expressed by activated lung and intestinal epithelial cells, keratinocytes, and fibroblasts. However, dendritic cells (DCs), mast cells, and presumably other immune cells can also produce TSLP. Different groups of investigators have demonstrated the existence of two variants for TSLP in human tissues: the main isoform expressed in steady state is the short form (sf TSLP), which plays a homeostatic role, whereas the long form (lfTSLP) is upregulated in inflammatory conditions. In addition, there is evidence that in pathological conditions, TSLP can be cleaved by several endogenous proteases. Several cellular targets for TSLP have been identified, including immune (DCs, ILC2, T and B cells, NKT and Treg cells, eosinophils, neutrophils, basophils, monocytes, mast cells, and macrophages) and non-immune cells (platelets and sensory neurons). TSLP has been originally implicated in a variety of allergic diseases (e.g., atopic dermatitis, bronchial asthma, eosinophilic esophagitis). Emerging evidence indicates that TSLP is also involved in chronic inflammatory (i.e., chronic obstructive pulmonary disease and celiac disease) and autoimmune (e.g., psoriasis, rheumatoid arthritis) disorders and several cancers. These emerging observations greatly widen the role of TSLP in different human diseases. Most of these studies have not used tools to analyze the expression of the two TSLP isoforms. The broad pathophysiologic profile of TSLP has motivated therapeutic targeting of this cytokine. Tezepelumab is a first-in-class human monoclonal antibody (1) that binds to TSLP inhibiting its interaction with TSLP receptor complex. Tezepelumab given as an add-on-therapy to patients with severe uncontrolled asthma has shown safety and efficacy. Several clinical trials are evaluating the safety and the efficacy of tezepelumab in different inflammatory disorders. Monoclonal antibodies used to neutralize TSLP should not interact or hamper the homeostatic effects of sf TSLP.

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“…IL-3 is allegedly the most potent growth factor for basophils, but it is not essential for their generation under physiological conditions as their incidence in the bone marrow is not impaired in IL-3-deficient mice. 18 Thymic stromal lymphopoietin (TSLP) at high concentrations can mimic the proliferative effect of IL-3 on basophils 19 and target the population residing in the bone marrow directly to elicit a population that promotes type 2 inflammation. 20 However, it seems that this effect required the presence of IL-3.…”

Section: Introductionmentioning

confidence: 99%