Thomas Volz

Technische Universität München, München, Bavaria, Germany

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Publications (31)142.9 Total impact

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    ABSTRACT: Die Haut ist das größte Organ an der Grenze zwischen Umwelt und Wirt. Sie spielt beim Schutz gegen Pathogene als physische Barriere, als erster Ort der Erkennung und als „Dirigent“ einer Reihe aufeinander folgender Immunreaktionen eine wichtige Rolle. Bei diesem Prozess ist eine Abstimmung zwischen ortsständigen Immunzellen in der Haut und zirkulierenden Immunzellen erforderlich. Früher wurde angenommen, dass die adaptive Immunantwort von B- und T-Lymphozyten durch festgelegte angeborene Immunreaktionen gesteuert wird. Heute wissen wir, dass unterschiedliche Immunreaktionen auf verschiedene Mikroorganismen durch ebenfalls variierende Reaktionen gesteuert werden müssen. Dies geschieht auf der Ebene der Ersterkennung eines Mikroorganismus durch Rezeptoren des angeborenen Immunsystems. Nur eine Feinregulierung des angeborenen Immunsystems ermöglicht die Steuerung von Immunreaktionen auf Mikrobiota bei Abwesenheit einer Entzündung sowie auf Pathogene im Kontext von Schutzreaktionen wie zum Beispiel Entzündungen. Wie genau das angeborene Immunsystem sich adaptiert, ist auch von Bedeutung für Krankheiten wie die atopische Dermatitis (AD) mit chronischer Entzündung. In diesem Übersichtsartikel zeigen wir, wie das angeborene Immunsystem seine Reaktionen feinreguliert und legen dabei einen Schwerpunkt auf die immunologischen Konsequenzen der kutanen angeborenen Immunerkennung durch TLR2. Diese neuen Erkenntnisse sind höchst relevant für das Verständnis des Mikrobiota-assoziierten Gesundheitszustands, der Immunabwehr und der Pathogenese chronisch kutaner Entzündungen, wie sie bei AD beobachtet werden.
    No preview · Article · Feb 2016 · Journal der Deutschen Dermatologischen Gesellschaft
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    ABSTRACT: The skin is the largest organ at the interface between environment and host. It plays a major protective role against pathogens as physical barrier, as site of first recognition, and as orchestrator of consecutive immune responses. In this process, immunological crosstalk between skin-resident and immune cells is required, and fixed innate immune responses were previously believed to orchestrate adaptive immunity of B and T lymphocytes. Today, we understand that diverse qualities of immune responses to different microbes need to be regulated by also varying responses at the level of first microbe recognition through receptors of the innate immune system. Only fine-tuning of the innate immune system allows for the orchestration of immune responses to the microbiota in the absence of inflammation as well as to pathogens in the context of protective responses including inflammation. Understanding how innate immunity precisely adapts is also important for diseases such as atopic dermatitis (AD) with chronic inflammation. In this review, we present data on how the innate immune system actually fine-tunes its responses with special focus on the immunological consequences of cutaneous innate immune sensing through TLR2. These new insights are highly relevant for understanding microbiota-associated state of health, immune defense, and the pathogenesis underlying chronic cutaneous inflammation as seen in AD.
    No preview · Article · Jan 2016 · Journal der Deutschen Dermatologischen Gesellschaft
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    ABSTRACT: The skin is the largest organ at the interface between the environment and the host. Consequently, the skin plays a central role in mounting effective host defense. In addition to pathogens, the microbiota and the host immune system are in permanent contact and communication via the skin. Consequences of this permanent interaction are a unique and partly symbiotic relationship, a tight interdependence between these partners, and also a functional "setting the clock," in which, in the healthy steady state, an induction of protective responses to pathogens is guaranteed. At the same time, commensal microbes contribute to the alertness of the immune system and to the maintenance of immune tolerance. Atopic dermatitis (AD) is a chronic inflammatory skin disease based on a complex genetic trait with defects in cutaneous barrier, in stabilizing skin integrity. Most of AD patients develop deviated innate and adaptive immune responses. As a result, increased susceptibility to cutaneous infection is found in AD patients, and the interactions between these microbes and the skin participate in the development of chronic cutaneous inflammation. The role of the adaptive immune system was characterized in much detail, less though the contribution of innate immunity to AD pathogenesis. It is rather recent evidence that demonstrates a dominant role of components of the innate immune system not only for protecting from microbial invasion but also by orchestrating chronic skin inflammation. In this review we discuss the role of innate immune signaling and consecutive immune networks important for the pathogenesis and management of AD.
    No preview · Article · Nov 2015 · Seminars in Immunopathology
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    ABSTRACT: Atopic dermatitis (AD) is a chronic inflammatory skin disease predominantly mediated by T helper cells. While numerous adaptive immune mechanisms in AD pathophysiology have been elucidated in detail, deciphering the impact of innate immunity in AD pathogenesis has made substantial progress in recent years and is currently a fast evolving field. As innate and adaptive immunity are intimately linked cross-talks between these two branches of the immune system are critically influencing the resulting immune response and disease. Innate immune recognition of the cutaneous microbiota was identified to substantially contribute to immune homeostasis and shaping of protective adaptive immunity in the absence of inflammation. Disturbances in the composition of the skin microbiome with reduced microbial diversity and overabundance of Staphylococcus spp. have been shown to be associated with AD inflammation. Distinct S. aureus associated microbial associated molecular patterns (MAMPs) binding to TLR2 heterodimers could be identified to initiate long lasting cutaneous inflammation driven by T helper cells and consecutively local immune suppression by induction of myeloid derived suppressor cells (MDSC) further favoring secondary skin infections as often seen in AD patients. Moreover dissecting cellular and molecular mechanisms in cutaneous innate immune sensing in AD pathogenesis paved the way for exploiting regulatory and anti-inflammatory pathways to attenuate skin inflammation. Activation of the innate immune system by MAMPs of non-pathogenic bacteria on AD skin alleviated cutaneous inflammation. The induction of tolerogenic dendritic cells, Interleukin-10 expression and regulatory Tr1 cells were shown to mediate this beneficial effect. Thus, activation of innate immunity by MAMPs of non-pathogenic bacteria for induction of regulatory T cell phenotypes seems to be a promising strategy for treatment of inflammatory skin disorders as atopic dermatitis. These new findings demons
    Full-text · Article · Jul 2015 · Frontiers in Immunology

  • No preview · Conference Paper · Mar 2015
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    ABSTRACT: Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ–producing TH1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12–producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4–mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/TH17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/TH17 responses without blocking IL-12/TH1, selective IL-4–mediated IL-23/TH17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12–dependent TH1 responses.
    No preview · Article · Feb 2015 · Proceedings of the National Academy of Sciences
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    ABSTRACT: The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.
    No preview · Article · Jan 2015 · Der Hautarzt

  • No preview · Conference Paper · Jan 2015
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    ABSTRACT: Skin is constantly exposed to bacteria and antigens, and cutaneous innate immune sensing orchestrates adaptive immune responses. In its absence, skin pathogens can expand, entering deeper tissues and leading to life-threatening infectious diseases. To characterize skin-driven immunity better, we applied living bacteria, defined lipopeptides, and antigens cutaneously. We found suppression of immune responses due to cutaneous infection with Gram-positive S. aureus, which was based on bacterial lipopeptides. Skin exposure to Toll-like receptor (TLR)2-6-binding lipopeptides, but not TLR2-1-binding lipopeptides, potently suppressed immune responses through induction of Gr1+CD11b+ myeloid-derived suppressor cells (MDSCs). Investigating human atopic dermatitis, in which Gram-positive bacteria accumulate, we detected high MDSC amounts in blood and skin. TLR2 activation in skin resident cells triggered interleukin-6 (IL-6), which induced suppressive MDSCs, which are then recruited to the skin suppressing T cell-mediated recall responses such as dermatitis. Thus, cutaneous bacteria can negatively regulate skin-driven immune responses by inducing MDSCs via TLR2-6 activation.
    Full-text · Article · Nov 2014 · Immunity
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    ABSTRACT: Atopic dermatitis (AD) is a T cell-mediated inflammatory skin disease, with TH2 cells initiating acute flares. This inflamed skin is immediately colonized with Staphylococcus aureus, which provides potent Toll-like receptor (TLR) 2 ligands. However, the effect of TLR2 ligands on the development of TH2-mediated AD inflammation remains unclear. We investigated the progression of TH2 cell-mediated dermatitis after TLR2 activation. Using models for acute AD with TH2 cells initiating cutaneous inflammation, we investigated the consequences of TLR2 activation. Dermatitis, as assessed by changes in ear skin thickness and histology, was analyzed in different BALB/c and C57BL/6 wild-type and knockout mouse strains, and immune profiling was carried out by using in vitro and ex vivo cytokine analyses. We show that TH2 cell-mediated dermatitis is self-limiting and depends on IL-4. Activation of TLR2 converted the limited TH2 dermatitis to chronic cutaneous inflammation. We demonstrate that the concerted activation of TLR2 and IL-4 receptor on dendritic cells is sufficient for this conversion. As an underlying mechanism, we found that the combinatorial sensing of the innate TLR2 ligands and the adaptive TH2 cytokine IL-4 suppressed anti-inflammatory IL-10 and consequently led to the exacerbation and persistence of dermatitis. Our data demonstrate that innate TLR2 signals convert transient TH2 cell-mediated dermatitis into persistent inflammation, as seen in chronic human AD, through IL-4-mediated suppression of IL-10. For the first time, these data show how initial AD lesions convert to chronic inflammation and provide another rationale for targeting IL-4 in patients with AD, a therapeutic approach that is currently under development.
    No preview · Article · Apr 2014 · The Journal of allergy and clinical immunology

  • No preview · Conference Paper · Mar 2014

  • No preview · Conference Paper · Mar 2014
  • Thomas Volz · Tilo Biedermann
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    ABSTRACT: During recent years our understanding how the innate immune system detects microbes and mounts a first and rapid immune response has grown tremendously. It has been shown that innate immunity not only represents the first line of defense but also initiates adaptive immune responses and orchestrates their different qualities that can be inflammatory or tolerogenic. Insights into these fundamental mechanisms of immune responses also helped to better understand the pathogenesis and disease course in atopic dermatitis. We know today that patients with atopic dermatitis most often present with defects in their skin barrier function, that lesions are heavily colonized with microbes, and that innate and adaptive immune responses are disturbed so that a vicious circle of self-amplifying skin inflammation develops. Detailed knowledge on the role of the innate immunity in general and its function in atopic dermatitis also helps to develop a new concept on disease mechanisms and therapeutic strategies some of which exploit immune pathways counter-balancing inflammation in atopic dermatitis. Based on the understanding of how the innate immune system functions, the current review provides insights to the clinician into the network of mechanisms as well as evolving therapeutic concepts in atopic dermatitis.
    No preview · Article · Dec 2013 · Allergo Journal: interdisziplinäre Zeitschrift für Allergologie und Umweltmedizin: Organ der Deutschen Gesellschaft für Allergie- und Immunitätsforschung
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    ABSTRACT: Beneficial effects of non-pathogenic bacteria are increasingly recognized. We reported in a placebo-controlled study with atopic dermatitis (AD) patients that cutaneous exposure to lysates of non-pathogenic bacteria alleviates skin inflammation. To now unravel underlying mechanisms, immune consequences of sensing non-pathogenic bacterium Vitreoscilla filiformis lysate (Vf) were characterized analyzing (i) differentiation of dendritic cells (DC) and, consecutively, (ii) effector functions of DC and Th cells in vitro and in a murine model of AD in NC/Nga mice in vivo. Topical treatment with Vf significantly reduced AD-like inflammation in NC/Nga mice. Importantly, cutaneous exposure to Vf in combination with the allergen FITC significantly reduced also subsequent allergen-induced dermatitis indicating active immune modulation. Indeed, innate sensing of Vf predominantly induced IL-10 producing DC, which was dependent on TLR2-activation. Vf-induced IL-10+ DC primed naïve CD4+ T helper cells to become regulatory IFN-γ(low) IL-10(high) Tr1 cells. These IL-10(high) Tr1 cells were also induced by Vf in vivo and strongly suppressed T effector cells and inflammation. In conclusion we show that innate sensing of non-pathogenic bacteria by TLR2 induces tolerogenic DC and regulatory Tr1 cells suppressing T effector cells and cutaneous inflammation. These findings indicate a promising therapeutic strategy for inflammatory skin diseases like AD.Journal of Investigative Dermatology accepted article preview online, 28 June 2013; doi:10.1038/jid.2013.291.
    Full-text · Article · Jun 2013 · Journal of Investigative Dermatology
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    ABSTRACT: The skin, hair and nail changes in four distinct ectodermal dysplasia syndromes are compared and reviewed. These syndromes comprise Christ-Siemens-Touraine syndrome; ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome; ankyloblepharon-ectodermal defects-cleft lip/palate syndrome and Rapp-Hodgkin syndrome. A comprehensive overview of the dermatological signs and symptoms in these syndromes was generated from the database of the Ectodermal Dysplasia Network Germany, the clinical findings in the patients seen in our department and an extensive review of the literature. The findings included abnormalities of skin, sweating, hair and nails. These clinical findings are discussed in relation to the underlying molecular defects known to play a role in these four ectodermal dysplasia syndromes.
    No preview · Article · Jul 2012
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    ABSTRACT: T-cell activation and the subsequent transformation of activated T cells into T-cell blasts require profound changes in cell volume. However, the impact of cell volume regulation for T-cell immunology has not been characterized. Here we studied the role of the cell-volume regulating osmolyte transporter Taut for T-cell activation in Taut-deficient mice. T-cell mediated recall responses were severely impaired in taut(-/-) mice as shown with B16 melanoma rejection and hapten-induced contact hypersensitivity. CD4(+) and CD8(+) T cells were unequivocally located within peripheral lymph nodes of unprimed taut(-/-) mice but significantly decreased in taut(-/-) compared with taut(+/+) mice following in vivo activation. Further analysis revealed that Taut is critical for rescuing T cells from activation-induced cell death in vitro and in vivo as shown with TCR, superantigen, and antigen-specific activation. Consequently, reduction of CD4(+) and CD8(+) T cells in taut(-/-) mice upon antigen challenge resulted in impaired in vivo generation of T-cell memory. These findings disclose for the first time that volume regulation in T cells is an element in the regulation of adaptive immune responses and that the osmolyte transporter Taut is crucial for T-cell survival and T-cell mediated immune reactions.
    No preview · Article · Apr 2012 · European Journal of Immunology

  • No preview · Conference Paper · Mar 2012

  • No preview · Conference Paper · Mar 2012
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    ABSTRACT: Abstract is missing (Letter).
    Full-text · Article · Feb 2012 · Acta Dermato-Venereologica
  • Thomas Volz · Susanne Kaesler · Tilo Biedermann
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    ABSTRACT: The innate immune system is based on pathogen recognition receptors that bind conserved microbial molecular structures, so called pathogen-associated molecular patterns (PAMPs). The characterization of the innate immune system was long based on a linear step-wise concept of recognition, activation pathways and effector defense mechanisms. Only more recently it was recognized that the innate immune system needs regulatory elements, sideways and crosstalks that allows it to fine tune and adapt its response. Thus, it is an emerging field within innate immunity research to try to understand how the immune outcome of innate immune sensing is regulated and why immune responses can be substantially different, even though the same PAMPs may have been 'sensed' at the surface organs such as the skin. Only the expansion of the innate immune system from 'pure' linear activation pathways to fine tuned and regulated innate immune networks allows us to integrate the generation of gradually accentuated and qualitatively different effector and tolerogenic immune responses. This article provides a review of the basic concepts and players of the innate immune system and will present some of the newer data defining the innate immune networks effectively regulating the immune homoeostasis and immune effector mechanisms with special focus on the skin as one of the organs involved in regulating the immune interface between the environment and the organism.
    No preview · Article · Jan 2012 · Experimental Dermatology