Memory regulatory T cells reside in human skin

The Journal of clinical investigation (Impact Factor: 13.22). 02/2014; 124(3). DOI: 10.1172/JCI72932
Source: PubMed


Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.

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Available from: Fran Sverdrup, Mar 03, 2015
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    • "Additionally, the skin is exposed to environmental irritants and damage from ultraviolet light exposure, and undergoes frequent traumatic injury and wound repair. Dysregulated immune responses in the skin result in a number of inflammatory disorders, including contact hypersensitivity, atopic dermatitis, psoriasis, and Pemphigus vulgaris, and it is therefore not surprising that as in the intestines, there is a large population of Treg cells in both mouse and human skin even in the absence of overt inflammation (12, 22, 44). In human peripheral blood, most Treg cells express functional skin-homing receptors such as the functional E-selectin ligand cutaneous lymphocyte antigen (CLA) and CCR4 (22, 23), and skin-tropic Treg cells in mouse have been defined based on their expression of P- and E-selectin ligands, CCR4 and CD103 (12, 13, 17). "
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    ABSTRACT: Foxp3(+) regulatory T cells (Treg cells) are essential for establishing and maintaining self-tolerance, and also inhibit immune responses to innocuous environmental antigens. Imbalances and dysfunction in Treg cells lead to a variety of immune-mediated diseases, as deficits in Treg cell function contribute to the development autoimmune disease and pathological tissue damage, whereas overabundance of Treg cells can promote chronic infection and tumorigenesis. Recent studies have highlighted the fact that Treg cells themselves are a diverse collection of phenotypically and functionally specialized populations, with distinct developmental origins, antigen-specificities, tissue-tropisms, and homeostatic requirements. The signals directing the differentiation of these populations, their specificities and the mechanisms by which they combine to promote organ-specific and systemic tolerance, and how they embody the emerging property of regulatory memory are the focus of this review.
    Frontiers in Immunology 07/2014; 5:333. DOI:10.3389/fimmu.2014.00333
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    • "The skin is an active immune organ in which the keratinocytes can no longer be considered as cells that have now died and have the only function of acting as a barrier against the external environment; rather, they must be considered as active components of the immunoregulatory network between the external environment, the resident cutaneous immune system, and the microbiota [45]. "
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    ABSTRACT: The Italian interest group (IG) on atopic eczema and urticaria is member of the Italian Society of Allergology and Immunology. The aim of our IG is to provide a platform for scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from atopic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion of Staphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin.
    BioMed Research International 07/2014; 2014. DOI:10.1155/2014/436921 · 1.58 Impact Factor

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