Dermal γδ T cells – What have we learned?

O’Brien, Rebecca L.; Born, Willi K.

doi:10.1016/j.cellimm.2015.01.011

Cited by 65 publications

(61 citation statements)

References 59 publications

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“…3D and Table S1). These repeated Vγ6 and Vδ1 sequences correspond to the “canonical” sequences previously reported for a population of γδ T cells generated predominantly during the perinatal period and localized to a particular set of tissues, notably the skin dermis (O'Brien and Born, 2015). The corresponding population from Aire -KO perinates universally displayed Vγ6 + chains with the canonical CDR3; the Vδ1 + chains also frequently (~⅔ of the time) had the canonical CDR3 sequence (Fig.…”

Section: Resultssupporting

confidence: 71%

“…However, in many systems, Tγδ17 cells have been found to play an “early responder” role, accumulating early in target tissues, where they serve to recruit neutrophils, shape the complexion of the response, and perhaps inhibit Tregs (Cua and Tato, 2010; Chien et al, 2014; O'Brien and Born, 2015; Petermann et al, 2010). Thus, their role in the Aire-less disease may be an early one, prior to the generation of anti-IL-17 autoAbs, consistent with their early localization in uveoretinal tissue.…”

Section: Discussionmentioning

confidence: 99%

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Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing γδ T Cells to Promote Immunologic Tolerance

et al. 2016

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SUMMARY Aire's primary mechanism of action is to regulate transcription of a battery of genes in medullary thymic epithelial cells (mTECs) and, consequently, negative selection of effector T cells and positive selection of regulatory T cells. We found that Aire-deficient mice had expanded thymic and peripheral populations of perinatally generated interleukin(IL)-17A+ Vγ6+Vδ1+ T cells, considered to be “early responders” to tissue stress and to drive inflammatory reactions. Aire-dependent control of Il7 expression in mTECs regulated the size of thymic IL-17A+Vγ6+Vδ1+ compartments. In mice lacking Aire and γδ T cells, certain tissues typically targeted in the “Aire-less” disease, notably the retina, were only minimally infiltrated. IL-17A+Vγ6+Vδ1+ cells were present in the retina of wild-type mice and expanded very early in Aire-deficient mice. A putatively parallel population of IL-17A+Vγ9+Vδ2+ T cells was increased in humans lacking Aire. Thus, Aire exerts multi-faceted control of autoimmunity that extends to a population of innate-like T cells.

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Section: Resultssupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing γδ T Cells to Promote Immunologic Tolerance

et al. 2016

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“…Based on the data presented here, we propose an additional, novel pathway that primarily involves γδT cells and NKT cells: After the formation of the tissue-bound IC in the target organ, NKT cells and γδT cells that are present in the skin become activated. Possibly three non-mutually exclusive mechanisms may lead to their activation: (i) γδT cells and NKT cells can be observed in the skin3435 and modulate inflammatory processes353637. Those cells may either directly contribute to inflammation38 or activate and, according to our results, attract neutrophils into the skin39.…”

Section: Discussionmentioning

confidence: 53%

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Bieber

Witte

Sun

et al. 2016

Sci Rep

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T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organspecific autoimmune disease, namely epidermolysis bullosa acquisita ( T cells are essential regulators of host defense and exhibit direct cytotoxic as well as regulatory properties. The presence or absence of pro-inflammatory compared with regulatory T cell subsets affects the development and outcome of inflammatory reactions. Misbalance of T cell populations leads to autoimmune disorders, including systemic lupus erythematosus (SLE), different autoimmune bullous dermatoses (AIBDs) and rheumatoid arthritis (RA) [1][2][3] . In these diseases, the contribution of T cells to antibody production and maintenance of the autoimmune response has clearly been demonstrated 4,5 . In recent decades, the understanding of autoantibody-induced tissue injury has greatly improved. However, the role of T cells during the effector phase of autoimmune skin blistering diseases, i.e., tissue injury and inflammation in the targeted organs, is not completely understood. In this study, we investigated the role of T cells during this phase, using a mouse model of epidermolysis bullosa acquisita (EBA), a prototypical organ-specific autoimmune disease 6,7 . EBA is caused by autoantibodies directed against type VII collagen (COL7), an integral component of anchoring fibrils 8 . Animal models, employing antibody transfer into mice 9,10 , have added to a greater understanding of the mechanisms leading to blistering in EBA 9,11,12 . Based on the current understanding of EBA pathogenesis, the effector phase of EBA is predominantly driven by neutrophils -their depletion leading to a complete absence of experimental EBA 13. With regard to T cell involvement during this phase, in vivo and in vitro data have been contradictory. In vivo data indicated a T cell-independent process: Transfer of total IgG isolated from rabbits that had been immunized with COL7 into T cell-deficient mice induced subepidermal blistering 9 . However, in that study, no wild-type control for evaluation of the extent of blistering was included. In other

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“…The first subset is found in lymphoid tissues and, like αβ-T cells, displays a highly diversified TCR repertoire 116 . The second γδ-T cell subset is intraepithelial and expresses a more restricted TCR repertoire 117,118 . This is particularly true in the skin and the female reproductive tract of mice, where the γδ-T cells are essentially homogeneous 115,119 .…”

Section: Innate Responses To Candida and Mycobacteria Speciesmentioning

confidence: 99%

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

Robinson

Huppler

2017

Cytokine

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Mycobacteria and Candida species include significant human pathogens that can cause localized or disseminated infections. Although these organisms may appear to have little in common, several shared pathways of immune recognition and response are important for both control and infection-related pathology. In this article, we compare and contrast the innate and adaptive components of the immune system that pertain to these infections in humans and animal models. We also explore a relatively new concept in the mycobacterial field: biological commensalism. Similar to the well-established model of Candida infection, Mycobacterial species colonize their human hosts in equilibrium with the immune response. Perturbations in the immune response permit the progression to pathologic disease at the expense of the host. Understanding the immune factors required to maintain commensalism may aid with the development of diagnostic and treatment strategies for both categories of pathogens.

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Dermal γδ T cells – What have we learned?

Cited by 65 publications

References 59 publications

Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing γδ T Cells to Promote Immunologic Tolerance

Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing γδ T Cells to Promote Immunologic Tolerance

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

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