The Experts below are selected from a list of 12168 Experts worldwide ranked by ideXlab platform
Jerry Y. Niederkorn - One of the best experts on this subject based on the ideXlab platform.
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Induction of Contrasuppressor Cells and Loss of Immune Privilege Produced by Corneal Nerve Ablation
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Sudha Neelam, Jessamee Mellon, Amber Wilkerson, Jerry Y. NiederkornAbstract:Purpose Severing of corneal nerves in preparation of corneal transplantation abolishes Immune Privilege of subsequent corneal transplants placed into either eye: a phenomenon termed sympathetic loss of Immune Privilege (SLIP). SLIP is due to the disabling of T regulatory cells (Tregs) by CD11c+ contrasuppressor (CS) cells. This study characterized the induction, function, and manipulation of CS cell activity and the effect of these cells on Tregs induced by anterior chamber-associated Immune deviation (ACAID).
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corneal transplantation and Immune Privilege
International Reviews of Immunology, 2013Co-Authors: Jerry Y. NiederkornAbstract:Corneal transplants have been successfully performed in human subjects for over 100 years and enjoy an Immune Privilege that is unrivaled in the field of transplantation. Immune Privilege is defined as the reduced incidence and tempo in the Immune rejection of corneal allografts compared to other categories of organ allografts performed under the same conditions. Skin allografts transplanted across various MHC or minor histocompatibility barriers undergo rejection in approximately 100% of the hosts. By contrast, orthotopic corneal allografts experience long-term survival in 50% to >90% of the hosts, depending on the histocompatibility barriers that confront the host. The capacity of corneal allografts to evade Immune rejection is attributable to multiple anatomical, physiological and immunoregulatory conditions that conspire to prevent the induction and expression of alloimmunity.
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ocular Immune Privilege and ocular melanoma parallel universes or immunological plagiarism
Frontiers in Immunology, 2012Co-Authors: Jerry Y. NiederkornAbstract:Evidence of Immune Privilege in the eye was recorded almost 140 years ago, yet interest in Immune Privilege languished for almost a century. However, the past 35 years have witnessed a plethora of research and a rekindled interest in the mechanisms responsible for Immune Privilege in the anterior chamber of the eye. This research has demonstrated that multiple anatomical, structural, physiological, and immunoregulatory processes contribute to Immune Privilege and remind us of the enormous complexity of this phenomenon. It is widely accepted that Immune Privilege is an adaptation for reducing the risk of Immune-mediated inflammation in organs such as the eye and brain whose tissues have a limited capacity to regenerate. Recent findings suggest that Immune Privilege also occurs in sites where stem cells reside and raise the possibility that Immune Privilege is also designed to prevent the unwitting elimination of stem cells by Immune-mediated inflammation at these sites. Uveal melanoma arises within the eye and as such, benefits from ocular Immune Privilege. A significant body of research reveals an intriguing parallel between the mechanisms that contribute to Immune Privilege in the eye and those strategies used by uveal melanoma cells to evade Immune elimination once they have disseminated from the eye and establish metastatic foci in the liver. Uveal melanoma metastases seem to have “plagiarized” the blueprints used for ocular Immune Privilege to create “ad hoc Immune Privileged sites” in the liver.
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High-risk corneal allografts and why they lose their Immune Privilege
Current Opinion in Allergy and Clinical Immunology, 2010Co-Authors: Jerry Y. NiederkornAbstract:Purpose of review Corneal allografts are routinely performed without HLA typing or systemic immunosuppressive drugs. However, certain conditions create high risks for Immune rejection. This review discusses recent insights into the mechanisms that rob the corneal allograft of its Immune Privilege.
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Immune Privilege of corneal allografts
Ocular Immunology and Inflammation, 2010Co-Authors: Jerry Y. Niederkorn, Frank D P LarkinAbstract:Multiple anatomical, physiological, and immunoregulatory factors contribute to the Immune Privilege of corneal allografts. These factors conspire to prevent the induction and expression of Immune responses to the histocompatibility antigens on the corneal allograft. Corneal allografts also elicit a dynamic immunoregulatory process that deviates the Immune response from a destructive pathway to one of tolerance. Together, these conditions create an Immune Privileged environment and promote corneal allograft survival. Corneal allografts enjoy Immune Privilege that is unrivaled in the field of transplantation. However, this Immune Privilege is neither universal nor immutable. Th is has led some to dismiss Immune Privilege of corneal allografts out of hand. Moreover, the success of renal, cardiac, and liver transplants has improved over the past 3 decades and has reached levels similar to corneal allografts — an observation that has further fueled protests that corneal allografts are no different than other organ allografts, and that Immune Privilege is a misnomer. However, comparing survival rates among these categories of allografts is a bit like comparing an apple to an orange. For the comparisons to be valid, we must either compare the survival of corneal allografts in patients treated with the same intense systemic immunosuppressive agents that are used in renal, cardiac, or liver transplant patients, or compare all four categories of patients when the only treatment is topical corticosteroids (i.e., the standard prophylactic therapy in keratoplasty patients). The latter proposition, of course, is absurd, but does emphasize the importance of including all of the parameters when making comparisons relating to Immune Privilege. Prospective studies in animal models have unequivocally shown that in the absence of antirejection drugs, corneal allografts have dramatically higher acceptance and long-term survival rates than other categories of allografts such as skin transplants.
Hayato Terayama - One of the best experts on this subject based on the ideXlab platform.
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contribution of il 12 il 35 common subunit p35 to maintaining the testicular Immune Privilege
PLOS ONE, 2014Co-Authors: Hayato Terayama, Takayuki Yoshimoto, Shuichi Hirai, Munekazu Naito, Ning Qu, Naoyuki Hatayama, Shogo Hayashi, Kana Mitobe, Junichi FurusawaAbstract:The testis is an organ with Immune Privilege. The comprehensive blood–testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body’s Immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus−induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various Immune responses, but their roles in testicular Immune Privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular Immune Privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular Immune Privilege, in part in an IL-35-dependent manner.
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Contribution of IL-12/IL-35 Common Subunit p35 to Maintaining the Testicular Immune Privilege
PLOS ONE, 2014Co-Authors: Hayato Terayama, Takayuki Yoshimoto, Shuichi Hirai, Munekazu Naito, Ning Qu, Naoyuki Hatayama, Shogo Hayashi, Kana Mitobe, Junichi Furusawa, Izuru MizoguchiAbstract:The testis is an organ with Immune Privilege. The comprehensive blood–testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body’s Immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus−induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various Immune responses, but their roles in testicular Immune Privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular Immune Privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular Immune Privilege, in part in an IL-35-dependent manner.
Junichi Furusawa - One of the best experts on this subject based on the ideXlab platform.
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contribution of il 12 il 35 common subunit p35 to maintaining the testicular Immune Privilege
PLOS ONE, 2014Co-Authors: Hayato Terayama, Takayuki Yoshimoto, Shuichi Hirai, Munekazu Naito, Ning Qu, Naoyuki Hatayama, Shogo Hayashi, Kana Mitobe, Junichi FurusawaAbstract:The testis is an organ with Immune Privilege. The comprehensive blood–testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body’s Immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus−induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various Immune responses, but their roles in testicular Immune Privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular Immune Privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular Immune Privilege, in part in an IL-35-dependent manner.
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Contribution of IL-12/IL-35 Common Subunit p35 to Maintaining the Testicular Immune Privilege
PLOS ONE, 2014Co-Authors: Hayato Terayama, Takayuki Yoshimoto, Shuichi Hirai, Munekazu Naito, Ning Qu, Naoyuki Hatayama, Shogo Hayashi, Kana Mitobe, Junichi Furusawa, Izuru MizoguchiAbstract:The testis is an organ with Immune Privilege. The comprehensive blood–testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body’s Immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus−induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various Immune responses, but their roles in testicular Immune Privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular Immune Privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular Immune Privilege, in part in an IL-35-dependent manner.
A W Taylor - One of the best experts on this subject based on the ideXlab platform.
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Neuroimmunomodulation and Immune Privilege: the role of neuropeptides in ocular immunosuppression.
Neuroimmunomodulation, 2020Co-Authors: A W TaylorAbstract:Regional immunoregulatory mechanisms insure that the most effective Immune defense mounted is in proportion with preserving unique tissue functionalities. Immune-Privileged tissues, such as the eye, are tissue sites of extreme regional immunoregulation. They have evolutionarily adapted several mechanisms to prevent the induction of inflammation within their tissue microenvironment. With over half a century of experimental examinations of ocular Immune Privilege, only recently have we come to understand that neuropeptides constitutively present in ocular tissues are part of the mechanisms of Immune Privilege.
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Negative regulators that mediate ocular Immune Privilege
Journal of Leukocyte Biology, 2018Co-Authors: A W Taylor, Tat Fong NgAbstract:The ocular microenvironment has adapted several negative regulators of inflammation to maintain Immune Privilege and health of the visual axis. Several constitutively produced negative regulators within the eye TGF-β2, α-melanocyte stimulating hormone (α-MSH), Fas ligand (FasL), and PD-L1 standout because of their capacity to influence multiple pathways of inflammation, and that they are part of promoting Immune tolerance. These regulators demonstrate the capacity of Immune Privilege to prevent the activation of inflammation, and to suppress activation of effector Immune cells even under conditions of ocular inflammation induced by endotoxin and autoImmune disease. In addition, these negative regulators promote and expand Immune cells that mediate regulatory and tolerogenic immunity. This in turn makes the Immune cells themselves negative regulators of inflammation. This provides for a greater understanding of Immune Privilege in that it includes both molecular and cellular negative regulators of inflammation. This would mean that potentially new approaches to the treatment of autoImmune disease can be developed through the use of molecules and cells as negative regulators of inflammation.
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ocular Immune Privilege and transplantation
Frontiers in Immunology, 2016Co-Authors: A W TaylorAbstract:Allografts are afforded a level of protection from rejection within Immune Privileged tissues. Immune Privileged tissues involve mechanisms that suppress inflammation, and promote Immune tolerance. There are anatomical features, soluble factors, membrane associated proteins, and alternative antigen presenting cells that contribute to allograft survival in the Immune Privileged tissue. This review presents the current understanding of how the mechanism of ocular Immune Privilege promote tolerogenic activity by antigen presenting cells, and T cells in response to the placement of foreign antigen within the ocular microenvironment. Discussed will be the unique anatomical, cellular and molecular mechanisms that lessen the chance for a graft destroying Immune responses within the eye. As more is understood about the molecular mechanisms of ocular Immune Privilege greater is the potential in using these molecular mechanisms in therapies to prevent allograft rejection.
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Ocular Immune Privilege in the Year 2010: Ocular Immune Privilege and Uveitis
Ocular Immunology and Inflammation, 2010Co-Authors: A W Taylor, Henry J. KaplanAbstract:The phrase “Immune Privilege” was coined by Peter Medawar to describe the absence of an Immune response to allografts placed into the anterior chamber of the eye or brain. We now understand that Immune Privilege is more than a passive microenvironment with a distinctive anatomical structure that holds back immunity. The ocular microenvironment actively engages the Immune system with immunosuppressive biochemical mechanisms. The unique characteristics of ocular Immune Privilege appear designed to protect the eye from damage while preserving foveal vision, thus providing the host with a definite survival advantage. However, the protection is not always sufficient and the eye becomes susceptible to uveitis. Uveitis is an intraocular inflammatory disorder that encompasses a wide range of underlying etiologies. It may be idiopathic or associated with systemic disease or infection. Understanding the biochemistry of Immune Privilege has the potential to identify its weaknesses that allow for immunity to break th...
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Ocular Immune Privilege
Eye, 2009Co-Authors: A W TaylorAbstract:It has been over 60 years since the phrase Immune Privilege was used by Sir Peter Medawar to describe the lack of an Immune response against allografts placed into the ocular microenvironment. Since then, we have come to understand that the mechanisms of ocular Immune Privilege include unique anatomical features of a blood barrier and a lack of direct lymphatic drainage. Also, we know that the ocular microenvironment is rich with immunosuppressive molecules that influence the activity of Immune cells. Moreover, the placement of foreign antigen into the ocular microenvironment can induce a systemic form of tolerance to the foreign antigen called anterior chamber-associated Immune deviation (ACAID). Many soluble immunomodulators are found in aqueous humour, and are a mixture of growth factors, cytokines, neuropeptides, and soluble receptors. This is a continuously growing list. The mechanisms of ocular Immune Privilege induce apoptosis, promote the production of anti-inflammatory cytokines, and mediate the activation of antigen-specific regulatory immunity. These mechanisms of Immune Privilege also attempt to impose themselves upon immunity within the uveitic eye. The adaptation of several anatomical and biochemical mechanisms to establish an Immune Privileged microenvironment within the eye makes the eye immunologically unique. It is a tissue site where we may learn how immunity is regulated in inflammation and at rest. Success in translating the lessons of ocular Immune Privilege to other tissues has the potential to drastically change the therapy and clinical outcomes of autoImmune diseases and allograft survival.
Takayuki Yoshimoto - One of the best experts on this subject based on the ideXlab platform.
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contribution of il 12 il 35 common subunit p35 to maintaining the testicular Immune Privilege
PLOS ONE, 2014Co-Authors: Hayato Terayama, Takayuki Yoshimoto, Shuichi Hirai, Munekazu Naito, Ning Qu, Naoyuki Hatayama, Shogo Hayashi, Kana Mitobe, Junichi FurusawaAbstract:The testis is an organ with Immune Privilege. The comprehensive blood–testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body’s Immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus−induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various Immune responses, but their roles in testicular Immune Privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular Immune Privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular Immune Privilege, in part in an IL-35-dependent manner.
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Contribution of IL-12/IL-35 Common Subunit p35 to Maintaining the Testicular Immune Privilege
PLOS ONE, 2014Co-Authors: Hayato Terayama, Takayuki Yoshimoto, Shuichi Hirai, Munekazu Naito, Ning Qu, Naoyuki Hatayama, Shogo Hayashi, Kana Mitobe, Junichi Furusawa, Izuru MizoguchiAbstract:The testis is an organ with Immune Privilege. The comprehensive blood–testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body’s Immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus−induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various Immune responses, but their roles in testicular Immune Privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular Immune Privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular Immune Privilege, in part in an IL-35-dependent manner.
