Serum leptin levels correlate negatively with the capacity of vitamin D to modulate the in vitro cytokines production by CD4+ T cells in asthmatic patients

Dias, Aleida S.O.; Santos, Isabelle C.L.; Delphim, Letícia; Fernandes, Gabriel; Endlich, Larissa R.; Cafasso, Marcos Octávio S D; Maranhão, Ana Lúcia; Silva, Sonia Regina da; Andrade, Regis M.; Agrawal, Anshu; Linhares, Ulisses C.; Bento, Cleonice A.M.

doi:10.1016/j.clim.2019.06.001

Cited by 9 publications

(13 citation statements)

References 98 publications

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“…The increased susceptibility to allergic asthma in obese individuals was also linked to a leptin-dependent increase of Th2 cell proliferation, activation, and survival ( Zheng et al, 2016 ), and elevated circulating leptin correlated with pro-allergic Th2 cell cytokine signatures and Th2 cell imbalance in children with allergic rhinitis and in patients with allergic asthma ( Dias et al, 2019 ; Zeng et al, 2018 ). The key immunopathological role of leptin in allergic reactions has also been linked to its effect on human eosinophils in which the engagement of the LEPR activates MAPK-dependent pathways, hampers the caspase cascade and cell death, and induces release of pro-inflammatory cytokines and chemokines ( Conus et al, 2005 ; Wong et al, 2007 ).…”

Section: The Role Of Leptin In Immunitymentioning

confidence: 99%

The pleiotropic roles of leptin in metabolism, immunity, and cancer

Candia

Prattichizzo

Garavelli

et al. 2021

Journal of Experimental Medicine

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The discovery of the archetypal adipocytokine leptin and how it regulates energy homeostasis have represented breakthroughs in our understanding of the endocrine function of the adipose tissue and the biological determinants of human obesity. Investigations on leptin have also been instrumental in identifying physio-pathological connections between metabolic regulation and multiple immunological functions. For example, the description of the promoting activities of leptin on inflammation and cell proliferation have recognized the detrimental effects of leptin in connecting dysmetabolic conditions with cancer and with onset and/or progression of autoimmune disease. Here we review the multiple biological functions and complex framework of operations of leptin, discussing why and how the pleiotropic activities of this adipocytokine still pose major hurdles in the development of effective leptin-based therapeutic opportunities for different clinical conditions.

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Section: The Role Of Leptin In Immunitymentioning

confidence: 99%

The pleiotropic roles of leptin in metabolism, immunity, and cancer

Candia

Prattichizzo

Garavelli

et al. 2021

Journal of Experimental Medicine

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“…Increased leptin and IL-6 levels in asthma patients have recently been identified in several studies, strengthening the link of these pro-inflammatory cytokines with airway inflammation in asthma [ 63 – 65 ].…”

Section: Adipose Tissue and Inflammationmentioning

confidence: 99%

“…Increased pro-inflammatory effects the link of these pro-inflammatory cytokines with airway inflammation in asthma [63][64][65].…”

Section: Reduces Release Of Reactive Oxygen Species and Cytotoxic T-cell Responsementioning

confidence: 99%

Obesity, Inflammation, and Severe Asthma: an Update

Sharma

Cowan

2021

Curr Allergy Asthma Rep

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Purpose of Review Obesity-associated difficult asthma continues to be a substantial problem and, despite a move to address treatable traits affecting asthma morbidity and mortality, it remains poorly understood with limited phenotype-specific treatments. The complex association between asthma, obesity, and inflammation is highlighted and recent advances in treatment options explored. Recent Findings Obesity negatively impacts asthma outcomes and has a causal link in the pathogenesis of adult-onset asthma. Imbalance in the adipose organ found in obesity favours a pro-inflammatory state both systemically and in airways. Obesity may impact currently available asthma biomarkers, and obesity-associated asthma specific biomarkers are needed. Whilst surgical weight loss interventions are associated with improvements in asthma control and quality of life, evidence for pragmatic conservative options are sparse. Innovative approaches tackling obesity-mediated airway inflammation may provide novel therapies. Summary The immunopathological mechanisms underlying obesity-associated asthma require further research that may lead to novel therapeutic options for this disease. However, weight loss appears to be effective in improving asthma in this cohort and focus is also needed on non-surgical treatments applicable in the real-world setting.

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“…27,28 Elevated leptinemia aggravates allergic diseases. 29,30 Kalmarzi et al 32 demonstrated an inverse correlation between plasma leptin levels and lung function in asthma patients. In the present study, even when paired with body mass index, higher plasma leptin levels were quantified in moderate and severe AA patients when compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

“… 31 , 32 In asthmatic patients, high leptin levels were inversely correlated with lung function in asthmatic patients. 32 In a recent study published by our group, 30 a direct correlation between AA severity with both plasma leptin concentrations and levels of IL‐5, IL‐6 and IL‐17, released by purified CD4 + T‐cells, was observed. Nonetheless, this study did not analyze the relationship between different CD4 + T cell phenotypes and AA severity.…”

Section: Introductionmentioning

confidence: 91%

Leptin favors Th17/Treg cell subsets imbalance associated with allergic asthma severity

Vollmer

Dias

Lopes

et al. 2022

Clinical & Translational All

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Background Obesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4+T‐cell subsets from lean, overweight and obese AA patients. Methods Mononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4+T‐cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese‐related leptin dose on cytokine production and Treg cell function in AA‐derived CD4+ T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese. Results AA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17‐like cells rather than classic Th2‐like cells. On the other hand, the frequencies of Th1‐like, Br1 cells and regulatory CD4+ T‐cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17‐like cells positively correlated with leptin levels, the frequencies of regulatory CD4+ T‐cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity‐related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4+ T cell cultures from lean AA patients. Conclusion In summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17‐like and Th2/Th17 cells and decreasing regulatory CD4+T cell subsets, being adverse effects probably mediated by leptin overproduction.

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Serum leptin levels correlate negatively with the capacity of vitamin D to modulate the in vitro cytokines production by CD4+ T cells in asthmatic patients

Cited by 9 publications

References 98 publications

The pleiotropic roles of leptin in metabolism, immunity, and cancer

The pleiotropic roles of leptin in metabolism, immunity, and cancer

Obesity, Inflammation, and Severe Asthma: an Update

Leptin favors Th17/Treg cell subsets imbalance associated with allergic asthma severity

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