How type‐2 dendritic cells induce Th2 differentiation: Instruction, repression, or fostering T cell‐T cell communication?

Allergy, Год журнала: 2024, Номер 80(2), С. 395 - 407

Опубликована: Сен. 26, 2024

Allergic disease is caused by the activation of allergen-specific CD4+ type-2 T follicular helper cells (Tfh2) and 2 (Th2) effector that secrete cytokines IL-4, IL-5, IL-9, IL-13 upon allergen encounter, thereby inducing IgE production B tissue inflammation. While it accepted priming differentiation naïve into Th2 requires presentation type dendritic (DC2s), underlying signals remain unidentified. In this review we focus on interaction between allergen-presenting DC2s in lymph node (LN), potential mechanisms which might instruct differentiation. We outline recent advances characterizing DC2 development heterogeneity. sensing current proposed differentiation, with specific consideration role how they contribute to each mechanism. Finally, assess publications reporting a detailed analysis DC-T cell interactions LNs support Together, these studies are starting shape our understanding key initial step allergic immune response.

Язык: Английский

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From allergy to oncology: Targeting IL‐4 to boost cancer immunotherapy

Allergy, Год журнала: 2024, Номер 79(10), С. 2890 - 2892

Опубликована: Июль 24, 2024

Cancer can shape the tumor microenvironment (TME) by activating immune suppressive pathways. This discovery has led to development of cancer immunotherapy drugs, which primarily target T lymphocytes and have been integrated into clinical practice over past decade. Conversely, therapies targeting tumor-associated macrophages (TAMs) have, thus far, yielded disappointing results, likely due a limited understanding underlying mechanisms their ontogenesis.1 LaMarche et al.2 recently shed further light on pro-tumorigenic myelopoiesis, revealing that this process is orchestrated type 2 cytokine interleukin-4 (IL-4), investigated potential role IL-4 inhibitors in small cohort patients with non-small cell lung (NSCLC). Using murine model human samples NSCLC, authors demonstrated combination cytokines derived from TME (mainly IL-6, VEGF-A, IL-18) synergistically stimulates bone marrow-resident basophils eosinophils produce IL-4. In turn, marrow was found reprogram transcription granulocyte-monocyte progenitors towards an immunosuppressive tumorigenic phenotype (Figure 1A). Consistently, knock-out receptor α (IL-4Rα) mice NSCLC significantly reduced burden reprogramming antitumor, inflamed state. Similar results were observed basophil depletion, abolished myelopoiesis. Based these findings, translated research designing phase 1b trial for relapsed/refractory who had progressed PD-1/PD-L1 blockade previously received chemotherapy and/or radiation. Checkpoint inhibitors, such as blockers, transformed therapy reactivating antitumoral responses, but less than half respond therapies, indicating significant need alternative treatments.2 study, treatment regimen involved administration IL-4Rα antagonist dupilumab every 3 weeks, while maintaining blocking. Dupilumab given subcutaneously starting 600 mg loading dose, followed 300 weeks total three administrations. While no treatment-related adverse events observed, upregulated proinflammatory helper 1-type IFNγ IL-12), circulating monocytes, resulted expansion plasma cells effector CD8+ 1B). more shift corresponded impressive benefit one out six included patients, achieved near-complete response after 9 months treatment. Both study's preclinical findings preliminary outcomes offer intriguing perspectives immunotherapy, could be explored across various fronts. Firstly, must extensively elucidated define scenarios most approach. Recent evidence indicates may exhibit role, particularly when induced checkpoint bolstering lymph nodes.3 Similarly, combinations agents warrants comprehensive investigation. Compared monotherapy, combined holds promise greater efficacy shifting balance TAMs toward populations. fosters recruitment activity cells, through positive feedback loop between requires IFN-γ.4 The pivotal IFN-γ consistent al.5 experimental CD4+ cell-induced inflammatory controlling immune-evasive tumors. Meanwhile, remarkable it plausible hypothesize targeted inhibition might represent just tip iceberg immunotherapy. Beyond restructuring TME, therapeutic strategy proposed study application not only also other types are susceptible inhibitors. Finally, IL-4-mediated cancer-bone axis involves molecular players (such JAK1 STAT6) These inhibited biologics molecules currently available or still under study,6 allowing us speculate future battle against will involve use arsenal atopic diseases, translating allergy oncology. would like thank Dr. Mattia Giovannini his invaluable advice Anna Globinska final design Figure 1. Open access publishing facilitated Universita degli Studi di Milano, part Wiley - CRUI-CARE agreement. supported funds "Current Research Annual Funding" Italian Ministry Health. declare they conflict interest disclose relation paper. None.

Язык: Английский

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Evolving therapies for atopic dermatitis: Bridging guidelines and practice

Annals of the Academy of Medicine Singapore, Год журнала: 2024, Номер 53(11), С. 641 - 643

Опубликована: Ноя. 29, 2024

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterised by dysregulated type 2 immune responses, barrier dysfunction and intense pruritus (itching). The disease burden of AD substantial, affecting at least 171 million individuals worldwide in 2019, representing 2.23% the global population.1 Among diseases, ranks highest burden, as measured disability-adjusted life-years (DALYs).2 Its profound impact on patients’ quality life, along with significant economic burdens, underscores its status major healthcare challenge.

Язык: Английский

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Natural Products as Modulators of Aryl Hydrocarbon Receptor Signaling in Atopic Dermatitis Management

Molecules, Год журнала: 2024, Номер 29(24), С. 5951 - 5951

Опубликована: Дек. 17, 2024

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by immune dysregulation, barrier dysfunction, and significant patient burden. Recent studies have highlighted the aryl hydrocarbon receptor (AhR) as promising therapeutic target for AD management because of its pivotal role in modulating responses maintaining integrity. The dysfunction AhR pathway has been linked to pathogenesis, emphasizing need therapies that can restore regulatory functions. Natural products emerged potential modulators are effective safe alternatives conventional treatments. Compounds such curcumin, resveratrol, quercetin, microbial metabolites demonstrated ability activate AhR, reduce inflammation, promote function. These natural agents fewer side effects enhance compliance compared with therapies, making them attractive candidates long-term management. integration targeting provides multifaceted approach alleviates symptoms, addresses underlying disease mechanisms, promotes sustainable improvements health. This review highlights their roles enhancing outcomes through novel integrative treatment strategies.

Язык: Английский

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