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Allergic rhinitis (AR) is a common chronic disease affecting hundreds of millions of individuals globally, characterized by paroxysmal sneezing, watery rhinorrhea, nasal pruritus, and nasal congestion. It severely impairs patients' quality of life and increases the risk of complications such as asthma and nasal polyps 1. These typical symptoms profoundly compromise patients' daily functioning. The core pathophysiological mechanism of AR revolves around a vicious cycle involving two interconnected processes: first, Th2 cell-mediated immune dysregulation, which drives persistent inflammation; second, dysfunction of the nasal mucosal epithelial barrier, manifested by disruption of tight junctions, which facilitates increased allergen penetration 2,3.Inflammatory cytokines damage the barrier, while barrier leakage exacerbates immune responses, forming an intractable pathological loop 4. Current therapeutic approaches for AR exhibit notable limitations 567. Symptomatic treatments such as intranasal corticosteroids and oral anti-allergic agents either focus on anti-inflammation with limited barrier repair capacity or merely provide transient symptom relief, neither achieving a cure 5. Allergen immunotherapy (AIT), though potentially diseasemodifying, is characterized by long treatment courses, potential risks, and limited applicability 6,7. A critical unaddressed issue is that existing therapies fail to simultaneously target both immune dysregulation and barrier disruption-two pivotal pathological links-leaving significant unmet clinical needs. Thus, developing an innovative therapy that safely and effectively achieves "dual repair of immunity and barrier function" to fundamentally disrupt AR's pathological cycle holds substantial clinical and scientific value. A critical unresolved issue is that existing therapies fail to simultaneously target both immune dysregulation and barrier disruption, which are two pivotal pathological mechanisms. While some emerging approaches, such as mesenchymal stem cell (MSC) -based therapies, can contribute to barrier repair, they do not comprehensively address both pathological aspects 8,9, For example, intraperitoneal MSC administration ameliorates allergic rhinitis in murine models by migrating to nasal and lung tissues and suppressing T helper (Th)2 immune responses 9, yet a significant unmet clinical need remains. Consequently, an innovative therapy capable of safely and effectively achieving dual repair of immunity and barrier function to fundamentally disrupt the pathological cycle of AR holds substantial clinical and scientific value.Platelet-rich plasma (PRP), a platelet concentrate prepared via centrifugation of autologous whole blood 8 10, releases abundant growth factors stored in α-granules (e.g., platelet-derived growth factor PDGF, Transforming growth factor-β1 TGF-β1, epidermal growth factor EGF, vascular endothelial growth factor VEGF, and insulin-like growth factor IGF) upon platelet activation 8 10. These factors act synergistically and have demonstrated efficacy in anti-inflammation, promoting cell proliferation, and enhancing angiogenesis in fields such as orthopedic repair, wound healing, and skin regeneration. Recent studies have revealed that PRP alleviates symptoms of atrophic rhinitis 91011121314 111213141516 and sinonasal polyps sinusitis 15 17 through multiple mechanisms, including promoting barrier repair, enhancing ciliary function, exerting anti-inflammatory effects, regulating collagen metabolism, and improving microcirculation, with favorable safety profiles. However, current evidence remains constrained by methodological variability, necessitating more high-quality studies to support its clinical application. Notably, no published research has explored PRP as a treatment for AR to date. Although MSC therapy has shown therapeutic efficacy in murine models of AR 8,9, PRP offers distinct and notable advantages.These include its autologous origin-eliminating the risk of immune rejection-and its abundant, naturally derived cocktail of growth factors, which can synergistically target the dual pathological hallmarks of AR: immune dysregulation and nasal epithelial barrier damage. Importantly, PRP-based interventions for AR do not involve MSCbased therapies, underscoring its unique role as a standalone therapeutic strategy. Given PRP's pleiotropic biological properties, we hypothesize that its unique characteristics align well with the therapeutic demand for "dual repair of immunity and barrier function" in AR. This article aims to systematically propose and validate this innovative hypothesis.This hypothesis posits that PRP may intervene in the pathological process of AR by synergistically acting through dual pathways of immune modulation and barrier repair, thereby reshaping nasal immune homeostasis (Figure 1).In the context of immune modulation, PRP may act through three primary pathways:(1) regulating mast cell activation and repair via factors like TGF-β1, (2) balancing the Th2/Th17/Treg axis to correct immune dysregulation, and (3) modulating neuroimmune interactions through components such as nerve growth factor (NGF) and (IL)-1 receptor antagonist (IL-1Ra). For barrier repair, PRP is hypothesized to promote structural regeneration (e.g., via PDGF, EGF, VEGF), mitigate damage through antiinflammatory and antioxidant effects, and optimize the microenvironment via microcirculation improvement and matrix remodeling. In the context of immune modulation, PRP may employ TGF-β1 to potentially inhibit excessive mast cell activation and facilitate their repair. It could also balance the Th2/Th17/Treg axis by promoting regulatory T cells (Tregs) and suppressing overactive Th2/Th17 cells. Furthermore, PRP may mitigate neurogenic inflammation, as nerve growth factor (NGF) could modulate neuronal neuropeptides and interleukin (IL)-1 receptor antagonist (IL-1Ra) might inhibit glial cells to reduce the production of pro-inflammatory neuropeptides. For barrier repair, PRP may utilize growth factors such as PDGF, EGF, and VEGF to promote epithelial regeneration by stimulating cell proliferation, cilia and the of tight thereby potentially to barrier repair. PRP may through of the could antioxidant might microcirculation via and and may support matrix remodeling. It is hypothesized that could disrupt the cycle of allergen penetration and chronic is a chronic nasal mucosal by with its core pathophysiological involving of on mast cells (e.g., and symptoms cell Th2 cells via cells which pro-inflammatory factors (e.g., to production cells chronic and of tight with cell in the nasal mucosal barrier function, promoting allergen penetration and on the of we hypothesize that PRP may intervene in disease through two modulation and barrier nasal immune this we as PRP's potential to anti-inflammation by in including the of mast of Th2/Th17/Treg and modulation of While PRP's anti-inflammatory are in wound and its role in AR remains a is not merely as as a process involving structural regeneration of the of damage via anti-inflammatory and antioxidant and of the repair microenvironment through microcirculation and matrix remodeling. Although PRP's have in atrophic rhinitis and skin its efficacy in the AR mucosal barrier to hypothesis is the of "dual which posits that the of two could disrupt the vicious cycle of immune dysfunction barrier damage immune in thereby a therapeutic PRP may immune modulation by regulating mast cell function, the Th2/Th17/Treg and neuroimmune to the cycle and immune are of AR inflammation; their activation (e.g., by releases and and on evidence wound and is that TGF-β1 in PRP a critical role in mast cell It activation and pro-inflammatory demonstrated that TGF-β1 the of and mast cells by and In allergic epithelial cells and act synergistically to mast a process by TGF-β1, thereby mucosal such as and that TGF-β1 and via also mast cell to inflammation, which may contribute to disease TGF-β1 may AR by the of or mast on the AR such as the of cytokines (e.g., which may with TGF-β1 to activation via or the balance of factors (e.g., For in an TGF-β1 might mast cell in of could promote and These factors the of role and the need to PRP's in AR the hypothesis that PRP activation through multiple regulatory potential this remains to in AR AR immune Th2/Th17 and PRP is in including TGF-β1, which is to promote on this we hypothesize that PRP may function as an immune in AR. cells via AR exhibit Th2/Th17/Treg and PRP balance by and modulating platelet activation drives allergic inflammation; PRP may immunity by platelet-derived exacerbates and dysregulation PRP's may balance by PRP also factors (e.g., that promote with While role in nerve is its modulation of neuronal efficacy neurogenic symptoms The PRP's While PRP of the anti-inflammatory receptor antagonist (IL-1Ra) to PRP this potential anti-inflammatory the risk that could AR the in AR is and the need for neuroimmune by and glial synergistically neurogenic mucosal barrier dysfunction is a of AR and PRP could barrier repair via growth factor repair, and microenvironment its efficacy in atrophic rhinitis we propose that the mechanism by PRP might promote regeneration of nasal and core in the of growth factors and cytokines in which and the microenvironment through and The of factors promoting collagen cell and angiogenesis the and of nasal mucosal epithelial and vascular endothelial effectively mucosal promoting ciliary and cell function, thereby improving and in models that PRP may mitigate barrier by potentially antioxidant including and to damage for proliferation, VEGF for and for in with This such as matrix repair and with the antiinflammatory of on its in PRP is hypothesized to microcirculation by and This could promote thereby and and improving and to for mucosal repair In matrix PRP collagen thereby and Furthermore, growth factors in such as epidermal growth factor and insulin-like growth may contribute to barrier repair by promoting tight and epithelial For has shown to barrier by to the receptor and pathways like which the of on This mechanism could to the nasal might the of tight (e.g., and thereby epithelial on in administration increased the of and its potential to nasal epithelial cell and in AR These align with PRP's role in repair through studies have also a in nasal PRP treatment a with mucosal metabolism, and PRP's capacity to optimize the repair microenvironment through on microcirculation, matrix and growth epithelial PRP allergic rhinitis through two immune modulation, by suppressing excessive mucosal Th2/Th17/Treg and regulating neuroimmune and barrier repair, through epithelial and microenvironment via growth factor It is to that the in research on tissues (e.g., and distinct AR. While provide a biological for they as a evidence for PRP's efficacy in AR. The applicability of the and context of the nasal in AR remains a of this hypothesis and the a a clinical on the dual pathways of and to systematically PRP's potential in AR PRP prepared via blood centrifugation for by for plasma and in a to growth factor with to for PRP with and on the of the a of in are to PRP's potential on immune and epithelial cells. mast cells with PRP in to its on and the of and of mast cell activation Furthermore, the of (e.g., and factors to the role of TGF-β1 in mast cell and repair focus on T cell to PRP's potential on distinct the and PRP T cells in PRP's potential on T cells in with to and cell and to and thereby the hypothesis that PRP can modulate the Th2/Th17/Treg balance neuroimmune and with PRP to its on (e.g., and glial cell activation (e.g., glial the role of For nasal mucosal epithelial cells to and with with clinical of PRP as a therapy nasal mucosal epithelial cells with PRP to in and to PRP's potential antioxidant capacity in an epithelial barrier repair a wound nasal epithelial cells (e.g., with PRP and of to PRP's to promote barrier repair, including structural regeneration and in an epithelial barrier repair a wound nasal epithelial cells (e.g., with PRP to the of epithelial wound and structural regeneration. in to the of the nasal epithelial and nasal epithelial cells the of with and the multiple to barrier while the of a the cell by in the of the tight and for both to the barrier repair, PRP's capacity to promote both the structural regeneration and of the nasal epithelial the in of the an AR via and to or and for inflammation, for for nasal mucosal These are to PRP can of immune dysregulation and barrier damage in a the in of the an AR by intraperitoneal of on and by intranasal to for both and three PRP autologous and PRP autologous daily intranasal for PRP prepared via and its platelet to that of whole blood to the and nasal daily to AR the for blood for and cytokines by nasal tissues for cell and the nasal mucosal These are to PRP can immune dysregulation and nasal epithelial barrier damage in AR and to the in of dual clinical is to the safety and of PRP in with AR to intranasal PRP by a focus on and like the and mucosal for in Th2 cytokines and tight to evidence for the can The a of a of with a of persistent allergic rhinitis AR have an to intranasal to either intranasal of autologous PRP in the or in the to and The a by a focus on and multiple focus on and multiple the of and well as such as and nasal the of nasal mucosal and of tight (e.g., mucosal in Th2 cytokines and to the and of this in and clinical to systematically the hypothesis of PRP's in AR. The studies the of which to and of AR remains intranasal corticosteroids by suppressing Th2 nasal mucosal and immune symptoms via receptor fail to repair the nasal mucosal allergen immunotherapy of treatment to immune and emerging while immune pathways have critical address to correct Th2/Th17/Treg and capacity to structural nasal mucosal of therapies simultaneously target the core AR the vicious cycle of This to an need for that modulation The core of this hypothesis is PRP as a therapy that through treatment via an dual of its multiple factors can simultaneously correct immune dysregulation Th2/Th17 promote regulatory T cells and the barrier epithelial This may disrupt the cycle and reduce PRP's autologous the immune of safety to current Furthermore, studies PRP regeneration in with dysfunction could by PRP could a therapeutic for three with AR with nasal polyps or and or are the safety of an that autologous PRP the risk of Furthermore, a this hypothesis is the on The while are by evidence in wound healing, and The and of pathways in the of AR in as in the clinical of PRP for AR significant which A primary is PRP its biological are not are on the Given that AR is characterized by and inflammation, the in could potentially the this hypothesis on which is to a more favorable safety by the risk of inflammation, though this remains to and of the of PRP with treatment a dual mechanism for immune barrier repair that the Th2/Th17/Treg axis an innovative to AR in and studies support its capacity and to the nasal mucosal barrier, yet high-quality clinical are to its efficacy and This hypothesis offers a on AR and a for developing therapies that address both the symptoms and of AR. Allergic rhinitis (AR) is a common chronic disease affecting hundreds of millions of individuals globally, characterized by paroxysmal sneezing, watery rhinorrhea, nasal pruritus, and nasal congestion. It severely impairs patients' quality of life and increases the risk of complications such as asthma and nasal polyps 1. These typical symptoms profoundly compromise patients' daily functioning. The core pathophysiological mechanism of AR revolves around a vicious cycle involving two interconnected processes: first, Th2 cell-mediated immune dysregulation, which drives persistent inflammation; second, dysfunction of the nasal mucosal epithelial barrier, manifested by disruption of tight junctions, which facilitates increased allergen penetration cytokines damage the barrier, while barrier leakage exacerbates immune responses, forming an intractable pathological loop 4. Current therapeutic approaches for AR exhibit notable limitations 567. Symptomatic treatments such as intranasal corticosteroids and oral anti-allergic agents either focus on anti-inflammation with limited barrier repair capacity or merely provide transient symptom relief, neither achieving a cure 5. Allergen immunotherapy (AIT), though potentially diseasemodifying, is characterized by long treatment courses, potential risks, and limited applicability 6,7. A critical unresolved issue is that existing therapies fail to simultaneously target both immune dysregulation and barrier disruption, which are two pivotal pathological mechanisms. While some emerging approaches, such as mesenchymal stem cell (MSC) -based therapies, can contribute to barrier repair, they do not comprehensively address both pathological aspects 8,9, For example, intraperitoneal MSC administration ameliorates allergic rhinitis in murine models by migrating to nasal and lung tissues and suppressing T helper (Th)2 immune responses 9, yet a significant unmet clinical need remains. Consequently, an innovative therapy capable of safely and effectively achieving dual repair of immunity and barrier function to fundamentally disrupt the pathological cycle of AR holds substantial clinical and scientific value.Platelet-rich plasma (PRP), a platelet concentrate prepared via centrifugation of autologous whole blood 10, releases abundant growth factors stored in α-granules (e.g., platelet-derived growth factor PDGF, Transforming growth factor-β1 TGF-β1, epidermal growth factor EGF, vascular endothelial growth factor VEGF, and insulin-like growth factor IGF) upon platelet activation 10. These factors act synergistically and have demonstrated efficacy in anti-inflammation, promoting cell proliferation, and enhancing angiogenesis in fields such as orthopedic repair, wound healing, and skin regeneration. Recent studies have revealed that PRP alleviates symptoms of atrophic rhinitis 111213141516 and sinonasal polyps 17 through multiple mechanisms, including promoting barrier repair, enhancing ciliary function, exerting anti-inflammatory effects, regulating collagen metabolism, and improving microcirculation, with favorable safety profiles. However, current evidence remains constrained by methodological variability, necessitating more high-quality studies to support its clinical application. Notably, no published research has explored PRP as a treatment for AR to date. Although MSC therapy has shown therapeutic efficacy in murine models of AR 8,9, PRP offers distinct and notable These include its autologous origin-eliminating the risk of immune rejection-and its abundant, naturally derived cocktail of growth factors, which can synergistically target the dual pathological hallmarks of AR: immune dysregulation and nasal epithelial barrier damage. Importantly, PRP-based interventions for AR do not involve therapies, underscoring its unique role as a standalone therapeutic strategy. Given PRP's pleiotropic biological properties, we hypothesize that its unique characteristics align well with the therapeutic demand for "dual repair of immunity and barrier function" in AR. This article aims to systematically propose and validate this innovative hypothesis.This hypothesis posits that PRP may intervene in the pathological process of AR by synergistically acting through dual pathways of immune modulation and barrier repair, thereby reshaping nasal immune homeostasis (Figure 1).In the context of immune modulation, PRP may act through three primary pathways:(1) regulating mast cell activation and repair via factors like TGF-β1, (2) balancing the Th2/Th17/Treg axis to correct immune dysregulation, and (3) modulating neuroimmune interactions through components such as nerve growth factor (NGF) and (IL)-1 receptor antagonist (IL-1Ra). For barrier repair, PRP is hypothesized to promote structural regeneration (e.g., via PDGF, EGF, VEGF), mitigate damage through antiinflammatory and antioxidant effects, and optimize the microenvironment via microcirculation improvement and matrix is a chronic nasal mucosal by with its core pathophysiological involving of on mast cells (e.g., and symptoms cell Th2 cells via cells which pro-inflammatory factors (e.g., to production cells chronic and of tight with cell in the nasal mucosal barrier function, promoting allergen penetration and on the of we hypothesize that PRP may intervene in disease through two modulation and barrier nasal immune this we as PRP's potential to anti-inflammation by in including the of mast of Th2/Th17/Treg and modulation of While PRP's anti-inflammatory are in wound and its role in AR remains a is not merely as as a process involving structural regeneration of the of damage via anti-inflammatory and antioxidant and of the repair microenvironment through microcirculation and matrix remodeling. Although PRP's have in atrophic rhinitis and skin its efficacy in the AR mucosal barrier to hypothesis is the of "dual which posits that the of two could disrupt the vicious cycle of immune dysfunction barrier damage immune in thereby a therapeutic may immune modulation by regulating mast cell function, the Th2/Th17/Treg and neuroimmune to the cycle and immune are of AR inflammation; their activation (e.g., by releases and and on evidence wound and is that TGF-β1 in PRP a critical role in mast cell It activation and pro-inflammatory demonstrated that TGF-β1 the of and mast cells by and In allergic epithelial cells and act synergistically to mast a process by TGF-β1, thereby mucosal such as and that TGF-β1 and via also mast cell to inflammation, which may contribute to disease TGF-β1 may AR by the of or mast on the AR such as the of cytokines (e.g., which may with TGF-β1 to activation via or the balance of factors (e.g., For in an TGF-β1 might mast cell in of could promote and These factors the of role and the need to PRP's in AR the hypothesis that PRP activation through multiple regulatory potential However, this remains to in AR immune Th2/Th17 and PRP is in including TGF-β1, which is to promote on this we hypothesize that PRP may function as an immune in AR. cells via AR exhibit Th2/Th17/Treg and PRP balance by and modulating platelet activation drives allergic inflammation; PRP may immunity by platelet-derived exacerbates and dysregulation PRP's may balance by PRP also factors (e.g., that promote with While role in nerve is its modulation of neuronal efficacy neurogenic symptoms The PRP's While PRP of the anti-inflammatory receptor antagonist (IL-1Ra) to PRP this potential anti-inflammatory the risk that could AR the in AR is and the need for neuroimmune by and glial synergistically neurogenic mucosal barrier dysfunction is a of AR and PRP could barrier repair via growth factor repair, and microenvironment its efficacy in atrophic rhinitis we propose that the mechanism by PRP might promote regeneration of nasal and core in the of growth factors and cytokines in which and the microenvironment through and The of factors promoting collagen cell and angiogenesis the and of nasal mucosal epithelial and vascular endothelial effectively mucosal promoting ciliary and cell function, thereby improving and in models that PRP may mitigate barrier by potentially antioxidant including and to damage for proliferation, VEGF for and for in with This such as matrix repair and with the antiinflammatory of on its in PRP is hypothesized to microcirculation by and This could promote thereby and and improving and to for mucosal repair In matrix PRP collagen thereby and Furthermore, growth factors in such as epidermal growth factor and insulin-like growth may contribute to barrier repair by promoting tight and epithelial For has shown to barrier by to the receptor and pathways like which the of on This mechanism could to the nasal might the of tight (e.g., and thereby epithelial on in administration increased the of and its potential to nasal epithelial cell and in AR These align with PRP's role in repair through studies have also a in nasal PRP treatment a with mucosal metabolism, and PRP's capacity to optimize the repair microenvironment through on microcirculation, matrix and growth epithelial PRP allergic rhinitis through two immune modulation, by suppressing excessive mucosal Th2/Th17/Treg and regulating neuroimmune and barrier repair, through epithelial and microenvironment via growth factor It is to that the in research on tissues (e.g., and distinct AR. While provide a biological for they as a evidence for PRP's efficacy in AR. The applicability of the and context of the nasal in AR remains a of this hypothesis and the a a clinical on the dual pathways of and to systematically PRP's potential in AR prepared via blood centrifugation for by for plasma and in a to growth factor with to for PRP with and on the of the a of in are to PRP's potential on immune and epithelial cells. mast cells with PRP in to its on and the of and of mast cell activation Furthermore, the of (e.g., and factors to the role of TGF-β1 in mast cell and repair focus on T cell to PRP's potential on distinct the and PRP T cells in with to and cell and to and thereby the hypothesis that PRP can modulate the Th2/Th17/Treg balance neuroimmune and with PRP to its on (e.g., and glial cell activation (e.g., glial the role of For nasal mucosal epithelial cells to and with with clinical of PRP as a therapy in and to PRP's potential antioxidant capacity in an epithelial barrier repair a wound nasal epithelial cells (e.g., with PRP to the of epithelial wound and structural in to the of the nasal epithelial and nasal epithelial cells the of with and the multiple to barrier while the of a the cell by in the of the tight and for both to the barrier repair, PRP's capacity to promote both the structural regeneration and of the nasal epithelial the in of the an AR by intraperitoneal of on and by intranasal to for both and three PRP autologous and PRP autologous daily intranasal for PRP prepared via and its platelet to that of whole blood to the and nasal daily to AR the for blood for and cytokines by nasal tissues for cell and the nasal mucosal These are to PRP can immune dysregulation and nasal epithelial barrier damage in AR and to the in of dual can The a of a of with a of persistent allergic rhinitis AR have an to intranasal to either intranasal of autologous PRP in the or in the to and The a by a focus on and multiple focus on and multiple the of and well as such as and nasal the of nasal mucosal and of tight (e.g., mucosal in Th2 cytokines and to the and of this in and clinical to systematically the hypothesis of PRP's in AR. The studies the of which to and of AR remains intranasal corticosteroids by suppressing Th2 nasal mucosal and immune symptoms via receptor fail to repair the nasal mucosal allergen immunotherapy of treatment to immune and emerging while immune pathways have critical address to correct Th2/Th17/Treg and to structural nasal mucosal of therapies simultaneously target the core AR the vicious cycle of This to an need for that modulation The core of this hypothesis is PRP as a therapy that through treatment via an dual of its multiple factors can simultaneously correct immune dysregulation Th2/Th17 promote regulatory T cells and the barrier epithelial This may disrupt the cycle and reduce PRP's autologous the immune of safety to current Furthermore, studies PRP regeneration in with dysfunction could by PRP could a therapeutic for three with AR with nasal polyps or and or are the safety of an that autologous PRP the risk of Furthermore, a this hypothesis is the on The while are by evidence in wound healing, and The and of pathways in the of AR in as in the clinical of PRP for AR significant which A primary is PRP its biological are not are on the Given that AR is characterized by and inflammation, the in could potentially the this hypothesis on which is to a more favorable safety by the risk of inflammation, though this remains to with as the of factors platelet α-granules the of to biological characteristics and and limitations in administration the need for of clinical and the applicability of PRP such as or is as a on its autologous is that this is in the of clinical A safety with AR and which a distinct disease The hypothesized for PRP could potentially to in in Consequently, is and clinical with AR to a safety this hypothesis a for AR the of PRP to research focus on three of critical to the regulatory of TGF-β1 and in PRP on to the nasal mucosal nasal mucosal to PRP efficacy and and of the of PRP with treatment a dual mechanism for immune barrier repair that the Th2/Th17/Treg axis an innovative to AR Current in and studies support its capacity and to the nasal mucosal barrier, yet high-quality clinical are to its efficacy and This hypothesis offers a on AR and a for developing therapies that address both the symptoms and of AR.
Tian et al. (Fri,) studied this question.