Protection and privilege

Waldmann, Herman

doi:10.1038/nature05165

Cited by 61 publications

(19 citation statements)

References 5 publications

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“…Lu et al (15) groundbreaking findings of mast cell dependent Treg function built on the observation that mast cell-related genes (e.g., mouse alpha-chymase, carboxypeptidase A3, tryptophan hydroxylase, and high affinity IgE receptor) were overexpressed in tolerant allografts and that tolerant grafts were always infiltrated with Treg and mast cells (38). Moreover, IL-9 is secreted by Treg cells, enhancing mast cell growth and chemotaxis and suggesting that Treg and mast cells form a functional unit that mediates graft tolerance (39). Lu et al (15) also demonstrated that immune tolerance to allogenic skin transplants could not be achieved in genetically engineered mast cell-deficient mice.…”

Section: Acute Rejectionmentioning

confidence: 96%

The Role of Mast Cells After Solid Organ Transplantation

et al. 2008

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Mast cells are best known as primary responders in allergic reactions, including anaphylaxis and asthma. However, recent studies have shown that mast cells are functionally diverse cells with immunoregulatory properties that influence both the innate and adaptive immunities. Mast cells are capable of producing an array of both proinflammatory and anti-inflammatory mediators, acting as antigen-presenting cells, and expressing a spectrum of costimulatory molecules. Moreover, mast cells seem to confer a certain degree of immune privilege to tissues in concert with T-regulatory cells and are essential players in fibrotic conditions. The following review of the literature serves to further define the role of mast cells in the immunologic reactions affecting transplanted solid organ grafts.

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Section: Acute Rejectionmentioning

confidence: 96%

The Role of Mast Cells After Solid Organ Transplantation

et al. 2008

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“…MCs are now appreciated to exert a dual immunoregulatory role [25]–[31], [34], [38], [48]: Under physiological circumstances, MCs may be primarily immuno-inhibitory, thus contributing to the maintenance of IP and peripheral tolerance [27], [31], [34], [37], [48]–[53] and therefore, possibly, to the maintenance of HF-IP [2], [53]. However, as MCs are primed to rapidly secrete proinflammatory ‘danger’ signals, their role can quickly convert into a tolerance-breaking, potentially autoimmunity-promoting one, such as during allograft rejection and EAE [25], [26], [31], [38], [39], [48], [52]–[54].…”

Section: Introductionmentioning

confidence: 99%

Abnormal Interactions between Perifollicular Mast Cells and CD8+ T-Cells May Contribute to the Pathogenesis of Alopecia Areata

Bertolini

Zilio²,

Rossi³

et al. 2014

PLoS ONE

129

130

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Alopecia areata (AA) is a CD8+ T-cell dependent autoimmune disease of the hair follicle (HF) in which the collapse of HF immune privilege (IP) plays a key role. Mast cells (MCs) are crucial immunomodulatory cells implicated in the regulation of T cell-dependent immunity, IP, and hair growth. Therefore, we explored the role of MCs in AA pathogenesis, focusing on MC interactions with CD8+ T-cells in vivo, in both human and mouse skin with AA lesions. Quantitative (immuno-)histomorphometry revealed that the number, degranulation and proliferation of perifollicular MCs are significantly increased in human AA lesions compared to healthy or non-lesional control skin, most prominently in subacute AA. In AA patients, perifollicular MCs showed decreased TGFβ1 and IL-10 but increased tryptase immunoreactivity, suggesting that MCs switch from an immuno-inhibitory to a pro-inflammatory phenotype. This concept was supported by a decreased number of IL-10+ and PD-L1+ MCs, while OX40L+, CD30L+, 4–1BBL+ or ICAM-1+ MCs were increased in AA. Lesional AA-HFs also displayed significantly more peri- and intrafollicular- CD8+ T-cells as well as more physical MC/CD8+ T-cell contacts than healthy or non-lesional human control skin. During the interaction with CD8+ T-cells, AA MCs prominently expressed MHC class I and OX40L, and sometimes 4–1BBL or ICAM-1, suggesting that MC may present autoantigens to CD8+ T-cells and/or co-stimulatory signals. Abnormal MC numbers, activities, and interactions with CD8+ T-cells were also seen in the grafted C3H/HeJ mouse model of AA and in a new humanized mouse model for AA. These phenomenological in vivo data suggest the novel AA pathobiology concept that perifollicular MCs are skewed towards pro-inflammatory activities that facilitate cross-talk with CD8+ T-cells in this disease, thus contributing to triggering HF-IP collapse in AA. If confirmed, MCs and their CD8+ T-cell interactions could become a promising new therapeutic target in the future management of AA.

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“…For the maintenance of immune privilege and induction of peripheral tolerance, secreted factors such as TGF-β1, α-MSH, and IL-10 play a key role, and the number of mechanisms that are exploited by immunologically privileged tissues to suppress or evade undesired (auto-) immune responses is ever increasing (58)(59)(60)(61). Recently, it has even been speculated that the rich endowment of the hair follicle's connective tissue sheath with mast cells may contribute to maintaining a low-level constitutive immune privilege of this skin appendage (62).…”

Section: Immune Privilege Collapsementioning

confidence: 99%

Lymphocytes, neuropeptides, and genes involved in alopecia areata

Gilhar¹,

Paus²,

Kalish³

2007

J. Clin. Invest.

272

278

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Many lessons in autoimmunity -particularly relating to the role of immune privilege and the interplay between genetics and neuroimmunology -can be learned from the study of alopecia areata, the most common cause of inflammation-induced hair loss. Alopecia areata is now understood to represent an organ-restricted, T cell-mediated autoimmune disease of hair follicles. Disease induction is associated with collapse of hair follicle immune privilege in both humans and in animal models. Here, the role of HLA associations, other immunogenetic factors, and neuroendocrine parameters in alopecia areata pathogenesis are reviewed. This instructive and clinically significant model disease deserves more widespread interest in the immunology community.Nonstandard abbreviations used: AA, alopecia areata; AIRE, autoimmune regulator; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; IP-10, IFN-g-inducible protein 10; MIC, MHC class I chain-related; MIF, macrophage migration inhibitory factor; α-MSH, α-melanocyte-stimulating hormone; NALP1, NACHT leucine-rich-repeat protein 1; NGF, nerve growth factor.

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Protection and privilege

Cited by 61 publications

References 5 publications

The Role of Mast Cells After Solid Organ Transplantation

The Role of Mast Cells After Solid Organ Transplantation

Abnormal Interactions between Perifollicular Mast Cells and CD8+ T-Cells May Contribute to the Pathogenesis of Alopecia Areata

Lymphocytes, neuropeptides, and genes involved in alopecia areata

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