Regulatory B cells protect against chronic hypoxia‐induced pulmonary hypertension by modulating the Tfh/Tfr immune balance

Li, Cheng; Liu, Pingping; Yao, Huiling; Zhu, Hao; Zhang, Shaoze; Meng, Fang; Li, San; Li, Guang; Peng, Yanping; Gu, Jing; Zhu, Liming; Jiang, Yongliang; Dai, Aiguo

doi:10.1111/imm.13589

Cited by 4 publications

(7 citation statements)

References 47 publications

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“…In SSc-PAH patients, circulating levels of CD24 hi CD27 + Bregs are decreased compared to SSc-no PAH patients [ 14 ]. HPH mice have decreased Breg levels in the spleen and peripheral blood, and decreased blimp-1 (a major Breg transcription factor) expression in the lungs [ 119 ]. Adoptive transfer of Bregs improves haemodynamics and pulmonary vascular remodelling in HPH mice.…”

Section: Effector Mechanisms Of B-cells In Pahmentioning

confidence: 99%

“…Preliminary evidence suggesting an efficacy of rituximab in PAH originated from animal studies. Indeed, anti-CD20 therapy improves haemodynamics, right ventricle hypertrophy and pulmonary vascular remodelling in several models of pulmonary hypertension [ 30 , 115 , 119 ]. Additionally, treatment limits immune complex deposition and IL-6, VEGF and hypoxia-induced factor-1α expression in the lungs of Sugen-5416/ovalbumin rats [ 115 ]; and annulled the increase in survival and proliferation observed in pulmonary artery endothelial cells incubated with MCT plasma [ 30 ].…”

Section: B-cell-targeted Therapies In Pahmentioning

confidence: 99%

“…Finally, these equivocal clinical findings may appear contradictory to experimental observations of rituximab efficacy. However, it should be noted that, in studies using animal models of pulmonary hypertension, anti-CD20 therapy was started at the time of disease induction, making it more of a prophylaxis than a curative treatment [ 30 , 115 , 119 ]. As such, rituximab could be an interesting option to prevent PAH occurrence in high-risk individuals such as CTD patients, or, alternatively, as an adjunctive therapy in select patients with the biomarkers suggesting rituximab-responsiveness.…”

Section: B-cell-targeted Therapies In Pahmentioning

confidence: 99%

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B-cells in pulmonary arterial hypertension: friend, foe or bystander?

Sanges,

Tian,

Dubucquoi

et al. 2024

Eur Respir J

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There is an unmet need for new therapeutic strategies that target alternative pathways to improve the prognosis of patients with pulmonary arterial hypertension (PAH). As immunity has been involved in the development and progression of vascular lesions in PAH, we review the potential contribution of B cells in its pathogenesis and evaluate the relevance of B cell-targeted therapies. Circulating B cell homeostasis is altered in PAH patients, with total B-cell lymphopenia, abnormal subset distribution (expansion of naïve and antibody-secreting cells, reduction of memory B cells) and chronic activation. B cells are recruited to the lungs through local chemokine secretion, and activated by several mechanisms: 1) interaction with lung vascular auto-antigens through cognate B cell receptors; 2) co-stimulatory signals provided by T follicular helper (Tfh) cells (IL-21), T helper 2 (Th2) cells and mast cells (IL-4, IL-6 and IL-13); and 3) increased survival signals provided by B cell activating factor (BAFF) pathways. This activity results in the formation of germinal centres within perivascular tertiary lymphoid organs and in the local production of pathogenic autoantibodies that target the pulmonary vasculature and vascular stabilization factors (including angiotensin-II/endothelin-1 receptors and bone morphogenetic protein receptors). B cells also mediate their effects through enhanced production of pro-inflammatory cytokines, reduced anti-inflammatory properties by regulatory B cells, IgG-induced complement activation, and IgE-induced mast cell activation. Precision-medicine approaches targeting B cell immunity are a promising direction for select PAH conditions, as suggested by the efficacy of anti-CD20 therapy in experimental models and a trial of rituximab in systemic sclerosis-associated PAH.

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Section: Effector Mechanisms Of B-cells In Pahmentioning

confidence: 99%

Section: B-cell-targeted Therapies In Pahmentioning

confidence: 99%

Section: B-cell-targeted Therapies In Pahmentioning

confidence: 99%

See 1 more Smart Citation

B-cells in pulmonary arterial hypertension: friend, foe or bystander?

Sanges,

Tian,

Dubucquoi

et al. 2024

Eur Respir J

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“…However, recent studies have suggested that a subset called regulatory B cells (Bregs) has additional functions including immunosuppression (93). Bregs have been shown to prevent HPH by regulating the immune balance of Tfh/Tfr and inhibiting the proliferation of PASMCs under hypoxic conditions (94).…”

Section: T Cells B Cells and Dcsmentioning

confidence: 99%

Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension

Wuren

2023

Front. Immunol.

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Hypoxic pulmonary hypertension (HPH) is a complicated vascular disorder characterized by diverse mechanisms that lead to elevated blood pressure in pulmonary circulation. Recent evidence indicates that HPH is not simply a pathological syndrome but is instead a complex lesion of cellular metabolism, inflammation, and proliferation driven by the reprogramming of gene expression patterns. One of the key mechanisms underlying HPH is hypoxia, which drives immune/inflammation to mediate complex vascular homeostasis that collaboratively controls vascular remodeling in the lungs. This is caused by the prolonged infiltration of immune cells and an increase in several pro-inflammatory factors, which ultimately leads to immune dysregulation. Hypoxia has been associated with metabolic reprogramming, immunological dysregulation, and adverse pulmonary vascular remodeling in preclinical studies. Many animal models have been developed to mimic HPH; however, many of them do not accurately represent the human disease state and may not be suitable for testing new therapeutic strategies. The scientific understanding of HPH is rapidly evolving, and recent efforts have focused on understanding the complex interplay among hypoxia, inflammation, and cellular metabolism in the development of this disease. Through continued research and the development of more sophisticated animal models, it is hoped that we will be able to gain a deeper understanding of the underlying mechanisms of HPH and implement more effective therapies for this debilitating disease.

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“…12 Among them, ODS has attracted great attention because it can remove refractory sulfur compounds under relatively mild conditions. 13,14 In the face of continuous fuel quality challenges, ODS has been proven to be an effective way to produce clean materials due to its strong ability for deep desulfurization, economy, and simplicity. 15,16 In order to achieve better desulfurization performance, it is necessary to develop efficient catalysts.…”

Section: Introductionmentioning

confidence: 99%