The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Firdaus S. Dhabhar - One of the best experts on this subject based on the ideXlab platform.
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Acute stress enhances while chronic stress suppresses Skin Immunity. The role of stress hormones and leukocyte trafficking.
Annals of the New York Academy of Sciences, 2006Co-Authors: Firdaus S. DhabharAbstract:Abstract: Delayed-type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses that, depending on the antigen, mediate beneficial (resistance to viruses, bacteria, fungi) or harmful (allergic dermatitis, autoImmunity) aspects of Immunity. Contrary to the widely held notion that stress is immunosuppressive, we have shown that under certain conditions, stress can enhance immune function. DTH reactions can be studied in rats or mice by challenging the pinnae of previously sensitized animals with antigen. studies have shown that acute stress administered immediately before antigen exposure significantly enhances Skin DTH. In contrast, chronic stress significantly suppresses Skin DTH. Stress-induced changes in leukocyte distribution may contribute to these bidirectional effects of stress, since acute stress induces a significant mobilization of leukocytes from the blood to the Skin, whereas chronic stress suppresses leukocyte mobilization. In order to identify the hormonal mediators of the observed effects of stress, we first showed that adrenalectomy (ADX) eliminates the stress-induced enhancement of DTH. Acute administration (to ADX animals) of low doses of corticosterone and/or epinephrine significantly enhances Skin DTH. In contrast, acute administration of high doses of corticosterone, low doses of dexamethasone, or chronic administration of moderate doses of corticosterone suppress Skin DTH. Thus, the timing and duration of stress may significantly affect the nature (enhancing versus suppressive) of the effects of stress on Skin immune function. These results suggest that during acute stress, stress hormones may help enhance immune function by informing the immune system about impending challenges (e.g., wounding or infection) that may be imposed by a stressor (e.g., an aggressor). Thus, during acute stress, the brain may send a warning signal to the immune system, just as it does to other fight/flight systems in the body.
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Stress, leukocyte trafficking, and the augmentation of Skin immune function.
Annals of the New York Academy of Sciences, 2003Co-Authors: Firdaus S. DhabharAbstract:Delayed type hypersensitivity (DTH) reactions represent cell-mediated immune responses that exert important immunoprotective (resistance to viruses, bacteria, and fungi) or immunopathologic (allergic or autoimmune hypersensitivity) effects. We have used the Skin DTH response as an in vivo model to study neuro-endocrine-immune interactions. We hypothesized that just as an acute stress response prepares the cardiovascular and musculoskeletal systems for fight or flight, it may also prepare the immune system for challenges (e.g., wounding) that may be imposed by a stressor (e.g., an aggressor). Studies showed that acute (2 hours) stress experienced before primary or secondary cutaneous antigen exposure induces significantly enhanced Skin DTH. This enhancement involves innate as well as adaptive immune mechanisms. Adrenalectomy eliminates the stress-induced enhancement of DTH. Acute administration of physiological concentrations of corticosterone and/or epinephrine to adrenalectomized animals enhances Skin DTH. Compared with those in controls, DTH sites from acutely stressed or hormone-injected animals show significantly greater erythema and induration, numbers of infiltrating leukocytes, and levels of cytokine gene expression. In contrast to acute stress, chronic stress is immunosuppressive. Chronic exposure to corticosterone or acute exposure to dexamethasone significantly suppresses Skin DTH. These results suggest that during acute stress, endogenous stress hormones enhance Skin Immunity by increasing leukocyte trafficking and cytokine gene expression at the site of antigen entry. Elucidation of mechanisms mediating a stress-induced enhancement of Skin immune function is important because such immunoenhancement can have protective (wound healing, resistance to infection) or pathological (allergic or autoimmune hypersensitivity) consequences.
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Enhancing versus suppressive effects of stress hormones on Skin immune function.
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Firdaus S. Dhabhar, Bruce S. McewenAbstract:Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoImmunity) aspects of immune function. Contrary to the idea that stress suppresses Immunity, we have reported that short-duration stressors significantly enhance Skin DTH and that a stress-induced trafficking of leukocytes to the Skin may mediate this immunoenhancement. Here, we identify the hormonal mediators of a stress-induced enhancement of Skin Immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of Skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced Skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed Skin DTH. These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.
Allyson L. Byrd - One of the best experts on this subject based on the ideXlab platform.
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non classical Immunity controls microbiota impact on Skin Immunity and tissue repair
Cell, 2018Co-Authors: Jonathan L. Linehan, Shurjo K. Sen, Jahangheer S. Shaik, Allyson L. Byrd, Oliver J Harrison, Seongji Han, Ivan Vujkoviccvijin, Alejandro V Villarino, Margery G SmelkinsonAbstract:Summary Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a Skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures. As such, non-classical MHCI-restricted commensal-specific immune responses not only promoted protection to pathogens, but also accelerated Skin wound closure. Thus, the microbiota can induce a highly physiological and pleiotropic form of adaptive Immunity that couples antimicrobial function with tissue repair. Our work also reveals that non-classical MHC class I molecules, an evolutionarily ancient arm of the immune system, can promote homeostatic Immunity to the microbiota.
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Contextual control of Skin Immunity and inflammation by Corynebacterium.
The Journal of experimental medicine, 2018Co-Authors: Vanessa K. Ridaura, Nicolas Bouladoux, Michael G. Constantinides, Samira Tamoutounour, Jan Claesen, Y. Erin Chen, Allyson L. Byrd, Eric D Merrill, Michael A. Fischbach, Yasmine BelkaidAbstract:How defined microbes influence the Skin immune system remains poorly understood. Here we demonstrate that Corynebacteria, dominant members of the Skin microbiota, promote a dramatic increase in the number and activation of a defined subset of γδ T cells. This effect is long-lasting, occurs independently of other microbes, and is, in part, mediated by interleukin (IL)-23. Under steady-state conditions, the impact of Corynebacterium is discrete and noninflammatory. However, when applied to the Skin of a host fed a high-fat diet, Corynebacterium accolens alone promotes inflammation in an IL-23-dependent manner. Such effect is highly conserved among species of Corynebacterium and dependent on the expression of a dominant component of the cell envelope, mycolic acid. Our data uncover a mode of communication between the immune system and a dominant genus of the Skin microbiota and reveal that the functional impact of canonical Skin microbial determinants is contextually controlled by the inflammatory and metabolic state of the host.
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Commensal–dendritic-cell interaction specifies a unique protective Skin immune signature
Nature, 2015Co-Authors: Shruti Naik, Christoph Wilhelm, Nicolas Bouladoux, Sean Conlan, Jonathan L. Linehan, Allyson L. Byrd, Oliver J Harrison, Seongji Han, Sarah Himmelfarb, Clayton DemingAbstract:The Skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local Immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate Skin Immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect Skin Immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier Immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of Skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the Skin immune system uses fluctuating commensal signals to calibrate barrier Immunity and provide heterologous protection against invasive pathogens. These findings reveal that the Skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific Immunity and pathologies.
Michael P. Schön - One of the best experts on this subject based on the ideXlab platform.
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who is really in control of Skin Immunity under physiological circumstances lymphocytes dendritic cells or keratinocytes
Experimental Dermatology, 2006Co-Authors: Jens-michael Schröder, Kristian Reich, Kenji Kabashima, Fu-tong Liu, Nikolaus Romani, Martin Metz, A. Kerstan, P. H. A. Lee, Karin Loser, Michael P. SchönAbstract:Abstract: Our views of the Skin Immunity theatre are undergoing constant change. These not only reflect paradigm shifts in general immunology and Skin biology, but also have profound clinical implications, which call for strategic changes in dermatological therapy. Nowhere can this be witnessed at a greater level of instructiveness and fascination than when addressing the question posed by this new Controversies feature. Thus, after a very long period of dominance by T cells and Langerhans cells as ‘lead actors’ on the Skin Immunity stage, the lowly keratinocyte has recently made an astounding theatrical appearance as a key protagonist of the innate Skin Immunity system, which may control even acquired Skin immune responses. Further enhancing dramatic complexity and tension, the mast cell has entered as an additional actor claiming centre stage, and the epidermal Langerhans cell has slipped in a surprise appearance as the chief agent of immunotolerance. May you, esteemed reader, enjoy the spectacle offered here by selected immunodermatology authorities who double as ‘stage managers’ pushing their respective favourite actors into the limelight. You get everything you may expect from a good performance – complete with the impresario's overture that lures you into the theatre and sets the stage, competing divas, recently discovered new talents and even the critic's digest while the performance is still ongoing. By the time the curtain drops, you will have reached your own, independent conclusions on how to answer the title question of this play – at least for the time being…
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Who is really in control of Skin Immunity under physiological circumstances – lymphocytes, dendritic cells or keratinocytes?
Experimental dermatology, 2006Co-Authors: Jens-michael Schröder, Kristian Reich, Kenji Kabashima, Fu-tong Liu, Nikolaus Romani, Martin Metz, A. Kerstan, P. H. A. Lee, Karin Loser, Michael P. SchönAbstract:Abstract: Our views of the Skin Immunity theatre are undergoing constant change. These not only reflect paradigm shifts in general immunology and Skin biology, but also have profound clinical implications, which call for strategic changes in dermatological therapy. Nowhere can this be witnessed at a greater level of instructiveness and fascination than when addressing the question posed by this new Controversies feature. Thus, after a very long period of dominance by T cells and Langerhans cells as ‘lead actors’ on the Skin Immunity stage, the lowly keratinocyte has recently made an astounding theatrical appearance as a key protagonist of the innate Skin Immunity system, which may control even acquired Skin immune responses. Further enhancing dramatic complexity and tension, the mast cell has entered as an additional actor claiming centre stage, and the epidermal Langerhans cell has slipped in a surprise appearance as the chief agent of immunotolerance. May you, esteemed reader, enjoy the spectacle offered here by selected immunodermatology authorities who double as ‘stage managers’ pushing their respective favourite actors into the limelight. You get everything you may expect from a good performance – complete with the impresario's overture that lures you into the theatre and sets the stage, competing divas, recently discovered new talents and even the critic's digest while the performance is still ongoing. By the time the curtain drops, you will have reached your own, independent conclusions on how to answer the title question of this play – at least for the time being…
Kenji Kabashima - One of the best experts on this subject based on the ideXlab platform.
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Role of Lymphoid Structure in Skin Immunity
Current topics in microbiology and immunology, 2020Co-Authors: Gyohei Egawa, Kenji KabashimaAbstract:The Skin is the outermost organ of the body and is exposed to many kinds of external pathogens. To manage this, the Skin contains multiple types of immune cells. To achieve sufficient induction of cutaneous adaptive immune responses, the antigen presentation/recognition in the Skin is an essential process. Recent studies have expanded our knowledge of how T cells survey their cognate antigens in the Skin. In addition, the formation of a lymphoid cluster, named inducible Skin-associated lymphoid tissue (iSALT), has been reported during Skin inflammation. Although iSALT may not be classified as a typical tertiary lymphoid organ, it provides specific antigen presentation sites in the Skin. In this article, we provide an overview of the antigen presentation mechanism in the Skin, with a focus on the development of iSALT and its function.
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The role of dendritic cells and macrophages in the Skin Immunity.
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 2016Co-Authors: Sachiko Ono, Kenji KabashimaAbstract:The Skin is one of the largest organs in the human body, which acts as the primary interface with the external world. In view of its protective role, mammalian Skin consists of physical and immunological barriers. The water-impermeable stratum corneum and the tight junctions in the granular layer work at the epidermal level work as the most important first and second "physical" barriers. Upon antigen invasion to the Skin, the integrated innate and acquired immune systems in both the epidermis and dermis are activated in a coordinated manner to neutralize the external intruder as the strong third "immunological" barriers. Dendritic cells and macrophages are known to play pivotal roles in such immunological barriers. Intra-vital analysis of the murine Skin by two-photon microscopy enabled us to assess the habituate and the direct interactions of various cells in the Skin in situ, which reside or infiltrate upon inflammation. We introduce the recent works how dendritic cells and macrophages orchestrate the Skin Immunity, highlighting the importance of sequential leucocyte cluster formation in the efficient activation of memory T cells in the Skin, which can be attributed as 'inducible Skin-associated lymphoid tissue (iSALT)'.
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Skin Immune System: Microanatomy
Encyclopedia of Immunobiology, 2016Co-Authors: Sachiko Ono, Kenji KabashimaAbstract:The Skin is equipped with three serial barriers that provide rapid and efficient protection against external intruders. The stratum corneum and tight junctions work at the level of epidermis as the first- and second-line ‘physical’ barriers. Beneath these barriers, the integrated immune systems in both epidermis and dermis act in a coordinated manner. This third-line ‘immunological’ barrier is composed of almost all cells in the Skin, including keratinocytes, Langerhans cells, dermal dendritic cells, macrophages, T cells, blood vessels, pericytes, and lymphatic vessels. In addition to focusing on the respective role of each cellular population, we describe about the concept of Skin-associated lymphoid tissue (SALT), which reminds us that the Skin is more than a peripheral site of inflammation but is a component of lymphatic system. To flesh out the concept of SALT, recent findings demonstrated the acquired multiple cell gathering under inflammation. The newly discovered phenomenon, which can be termed as inducible SALT (iSALT), exhibits the importance of direct cell–cell interaction in the Skin Immunity.
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Novel insights into the role of immune cells in Skin and inducible Skin-associated lymphoid tissue (iSALT)
Allergo Journal International, 2015Co-Authors: Sachiko Ono, Kenji KabashimaAbstract:The Skin is equipped with serial barriers that provide rapid and efficient protection against external intruders. Beneath the epidermal physical barriers of the stratum corneum and the tight junctions, the integrated immune systems in both the epidermis and the dermis act in a coordinated manner to protect the host. This “immunological” barrier is composed of various cells, including Skin-resident cells, such as keratinocytes, dendritic cells, tissue-resident macrophages, resident memory T cells, mast cells, and innate lymphoid cells. Additionally, infiltrating memory T cells, monocytes, neutrophils, basophils, and eosinophils are recruited in support of the host Immunity. In addition to discussing the role of each of these cellular populations, we describe the concept of Skin associated lymphoid tissue (SALT), which reminds us that the Skin is an important component of the lymphatic system. We further describe the newly discovered phenomenon of multiple cell gathering under Skin inflammation, which can be referred to as inducible SALT (iSALT). iSALT contributes to our understanding of SALT by highlighting the importance of direct cell-cell interaction in Skin Immunity.
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who is really in control of Skin Immunity under physiological circumstances lymphocytes dendritic cells or keratinocytes
Experimental Dermatology, 2006Co-Authors: Jens-michael Schröder, Kristian Reich, Kenji Kabashima, Fu-tong Liu, Nikolaus Romani, Martin Metz, A. Kerstan, P. H. A. Lee, Karin Loser, Michael P. SchönAbstract:Abstract: Our views of the Skin Immunity theatre are undergoing constant change. These not only reflect paradigm shifts in general immunology and Skin biology, but also have profound clinical implications, which call for strategic changes in dermatological therapy. Nowhere can this be witnessed at a greater level of instructiveness and fascination than when addressing the question posed by this new Controversies feature. Thus, after a very long period of dominance by T cells and Langerhans cells as ‘lead actors’ on the Skin Immunity stage, the lowly keratinocyte has recently made an astounding theatrical appearance as a key protagonist of the innate Skin Immunity system, which may control even acquired Skin immune responses. Further enhancing dramatic complexity and tension, the mast cell has entered as an additional actor claiming centre stage, and the epidermal Langerhans cell has slipped in a surprise appearance as the chief agent of immunotolerance. May you, esteemed reader, enjoy the spectacle offered here by selected immunodermatology authorities who double as ‘stage managers’ pushing their respective favourite actors into the limelight. You get everything you may expect from a good performance – complete with the impresario's overture that lures you into the theatre and sets the stage, competing divas, recently discovered new talents and even the critic's digest while the performance is still ongoing. By the time the curtain drops, you will have reached your own, independent conclusions on how to answer the title question of this play – at least for the time being…
Jonathan L. Linehan - One of the best experts on this subject based on the ideXlab platform.
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Abstract PR16: Mucosal-associated invariant T-cells respond to the cutaneous microbiota and promote Skin Immunity
Microbiome and Metabolism, 2019Co-Authors: Michael G. Constantinides, Samira Tamoutounour, Jonathan L. Linehan, Shurjo K. Sen, Jahangheer S. Shaik, Sobhan Roy, Erin J. Adams, Yasmine BelkaidAbstract:Infectious agents are estimated to cause approximately 18% of cancers worldwide, supporting a link between microbial products and carcinogenesis. The diverse array of commensal microorganisms that reside at barrier sites of the human body, collectively termed the microbiome, provide the primary source of constitutive microbial stimulation and promote immune homeostasis through their release of microbial products, including derivatives of vitamin synthesis. Mucosal-associated invariant T (MAIT) cells are unconventional T-cells that recognize microbial-derived metabolites and provide an initial defense to pathogens through their rapid production of type-1 or type-17 cytokines. While MAIT-cells have been shown to infiltrate colorectal tumors, it remains to be determined how MAIT-cells contribute to tumorigenesis and whether commensals regulate MAIT-cell function. Here we show that MAIT-cells are a substantial Skin-resident population capable of producing IL-17A. IL-23 signaling promotes the accumulation of cutaneous MAIT-cells and Skin commensals induce local MAIT-cell proliferation and IL-1-dependent IL-17A production. In the absence of commensals, MAIT-cells are dramatically decreased, indicating that the microbiota is necessary for the development of this population. Utilizing MAIT-cell-deficient mice, we demonstrate that cutaneous MAIT-cells promote wound healing and inhibit the colonization of pathogens. This work identifies MAIT-cells as the only cell population that is entirely dependent on the microbiota and reveals the mechanism by which these cells respond to the commensal microbial community. Since IL-17A promotes tumor vascularization and neutrophil recruitment, the high frequency of MAIT-cells in human Skin suggests that modulation of the Skin-resident bacteria may have clinical applications for the progression of melanoma, and current studies are exploring this possibility using the B16 melanoma model in mice.This work was supported by the NIH Intramural Research Program. MGC is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute. Citation Format: Michael G. Constantinides, Samira Tamoutounour, Jonathan L. Linehan, Shurjo Sen, Jahangheer Shaik, Sobhan Roy, Erin J. Adams, Yasmine Belkaid. Mucosal-associated invariant T-cells respond to the cutaneous microbiota and promote Skin Immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr PR16.
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non classical Immunity controls microbiota impact on Skin Immunity and tissue repair
Cell, 2018Co-Authors: Jonathan L. Linehan, Shurjo K. Sen, Jahangheer S. Shaik, Allyson L. Byrd, Oliver J Harrison, Seongji Han, Ivan Vujkoviccvijin, Alejandro V Villarino, Margery G SmelkinsonAbstract:Summary Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a Skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures. As such, non-classical MHCI-restricted commensal-specific immune responses not only promoted protection to pathogens, but also accelerated Skin wound closure. Thus, the microbiota can induce a highly physiological and pleiotropic form of adaptive Immunity that couples antimicrobial function with tissue repair. Our work also reveals that non-classical MHC class I molecules, an evolutionarily ancient arm of the immune system, can promote homeostatic Immunity to the microbiota.
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Commensal–dendritic-cell interaction specifies a unique protective Skin immune signature
Nature, 2015Co-Authors: Shruti Naik, Christoph Wilhelm, Nicolas Bouladoux, Sean Conlan, Jonathan L. Linehan, Allyson L. Byrd, Oliver J Harrison, Seongji Han, Sarah Himmelfarb, Clayton DemingAbstract:The Skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local Immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate Skin Immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect Skin Immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier Immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of Skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the Skin immune system uses fluctuating commensal signals to calibrate barrier Immunity and provide heterologous protection against invasive pathogens. These findings reveal that the Skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific Immunity and pathologies.