Asthma-Associated Long TSLP Inhibits the Production of IgA

Heerden, Dorianne van; Binnendijk, Robert S. van; Tromp, Samantha A.M.; Savelkoul, H.F.J.; Neerven, R. J. Joost van; Hartog, Gerco den

doi:10.3390/ijms22073592

Cited by 7 publications

(6 citation statements)

References 49 publications

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“…However, since the expression patterns and biological properties of these two different isoforms of TSLP seem to be distinct, these two TSLP isoforms should be analyzed separately in future studies. This is highlighted by findings in asthma research, where it was observed that the asthma-associated long TSLP isoform negatively regulates the secretion of IgA, potentially impacting the surveillance of mucosal surfaces detrimentally in this condition [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: a systematic review and meta-analysis

García-Reyes,

Zumaya-Pérez,

Pastelin-Palacios

et al. 2023

Clin Exp Med

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Thymic stromal lymphopoietin (TSLP) is critical in developing allergic responses, including atopic dermatitis (AD). We systematically reviewed the literature to complete a meta-analysis to quantitatively summarize the levels of serum TSLP in AD. The study was prospectively registered in the PROSPERO database (ID = CRD42021242628). The PUBMED, SCOPUS, and Cochrane Library databases were reviewed, and original articles investigating serum TSLP in AD patients were included. Differences in TSLP levels of AD patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying the Newcastle‒Ottawa Scale. Fourteen studies, which included 1,032 AD patients and 416 controls, were included. Meta-analysis showed that TSLP levels were significantly higher in the AD group than in the control group (SMD = 2.21, 95% CI 1.37–3.06, p < 0.001). Stratification by geographical region, age, disease severity, TSLP determination method, sample size, and study quality revealed significantly elevated TSLP levels in European AD patients (SMD = 3.48, 95% CI 1.75–5.21, p < 0.0001), adult AD patients (SMD = 4.10, 95% CI 2.00–6.21, p < 0.0001), child AD patients (SMD = 0.83, 95% CI 0.08–1.59, p = 0.031), and all severity groups with AD compared with the control group (mild: SMD = 1.15, 95% CI 0.14–2.16, p = 0.025; moderate: SMD = 2.48, 95% CI 0.33–4.62, p = 0.024; and severe: SMD = 8.28, 95% CI 4.82–11.74, p = 2.72e−6). Noticeably, adults showed higher serum TSLP levels than children with AD, and serum TSL levels increased according to AD severity. In conclusion, our meta-analysis demonstrates that circulating TSLP levels are elevated in patients with AD. Future studies are warranted to further elucidate the sources of heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: a systematic review and meta-analysis

García-Reyes,

Zumaya-Pérez,

Pastelin-Palacios

et al. 2023

Clin Exp Med

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“…An asthma-associated long form of TSLP is produced by epithelial cells following viral infection. It inhibits the production of IgA antibodies, which are believed to neutralise viruses at mucosal surfaces [ 48 ]. Viral infection also disrupts junctional complexes and inhibits wound repair, further reducing barrier integrity and driving the cycle of epithelial damage [ 49 – 51 ].…”

Section: Airway Epithelial Barrier Disruptionmentioning

confidence: 99%

The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma

Russell,

Boulet,

Brightling

et al. 2024

Eur Respir J

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Asthma is a disease of heterogeneous pathology, typically characterized by excessive inflammatory and bronchoconstrictor responses to the environment. The clinical expression of the disease is a consequence of the interaction between environmental factors and host factors over time, including genetic susceptibility, immune dysregulation and airway remodelling. As a critical interface between the host and the environment, the airway epithelium plays an important role in maintaining homeostasis in the face of environmental challenges. Disruption of epithelial integrity is a key factor contributing to multiple processes underlying asthma pathology. In this review, we first discuss the unmet need in asthma management and provide an overview of the structure and function of the airway epithelium. We then focus on key pathophysiological changes that occur in the airway epithelium, including epithelial barrier disruption, immune hyperreactivity, remodelling, mucus hypersecretion and mucus plugging, highlighting how these processes manifest clinically and how they might be targeted by current and novel therapeutics.

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“…Retinoic acid also promotes the production of IgA in the presence of loTSLP and may, thus, be able to restore IgA production in asthma patients in the presence of aberrant TSLP signaling. The addition of shTSLP or loTSLP did not affect B cell proliferation, neither in the presence nor the absence of CphosphodiestericG (CpG) [ 48 ].…”

Section: Tslp In Epithelium-driven Airways Inflammationmentioning

confidence: 99%

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy

Bagnasco,

De Ferrari,

Bondi

et al. 2024

IJMS

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Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.

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Asthma-Associated Long TSLP Inhibits the Production of IgA

Cited by 7 publications

References 49 publications

Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: a systematic review and meta-analysis

Serum thymic stromal lymphopoietin (TSLP) levels in atopic dermatitis patients: a systematic review and meta-analysis

The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy

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