Mast cells are required for phototolerance induction and scratching abatement

Self Cite

Psoralen and UVA (PUVA) has immunosuppressive and proapoptotic effects, which are thought to be responsible alone or in combination for its therapeutic efficacy. However, the molecular mechanism by which PUVA mediates its effects are not well understood. Activation of the serotonin (5-hydroxytryptamine, 5-HT) pathway has been suggested to be involved in the modulation of T cell responses and found to mediate UVB-induced immune suppression. In particular, the activation of the 5-HT2A receptor has been proposed as one mechanism responsible for UV-induced immune suppression. We therefore hypothesized that 5-HT may play a role in PUVA-induced effects. The model of systemic suppression of delayed-type hypersensitivity (DTH) to Candida albicans was used to study immune function after exposure of C3H and KITW-Sh/W-Sh mice to a minimal inflammatory dose of topical PUVA. The intraperitoneal injection of the 5-HT2 receptor antagonist ketanserin or cyproheptadine or an anti-5-HT antibody immediately before PUVA exposure entirely abrogated suppression of DTH but had no significant effect on inflammation, as measured by swelling and cellular infiltration of the skin, and apoptosis as determined by the number of sunburn cells in C3H mice. Importantly, the systemic injection of 5-HT recapitulated PUVA immune suppression of DTH but did not induce inflammation or apoptosis in the skin. KITW-Sh/W-Sh mice (exhibiting myelopoietic abnormalities, including lack of 5-HT-containing mast cells) were resistant to PUVA-induced suppression of DTH but not local skin swelling. Thus, this points towards a crucial role of 5-HT signaling in PUVA-induced immune suppression but not inflammation or apoptosis in situ in the skin.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Serotonin signalling is crucial in the induction of PUVA‐induced systemic suppression of delayed‐type hypersensitivity but not local apoptosis or inflammation of the skin

Wolf

Byrne

Limón-Flores

et al. 2016

Self Cite

“…MCs have been suggested to play a role in PLE, and their number in the papillary dermis is increased after photohardening with PUVA . Along with this, MC‐ deficiency is associated with UV‐provoked itching . Including the data on MCs and UV tolerance (see below), it is possible that MC dysfunction is important in the development of PLE .…”

Section: The Role Of Mast Cells In Uv‐driven Diseasesmentioning

confidence: 99%

Ultraviolet radiation and skin mast cells: Effects, mechanisms and relevance for skin diseases

Siiskonen

Smorodchenko

Krause

et al. 2017

Mast cells (MCs) are well known as versatile effector cells in allergic reactions and several other immune responses. Skin MCs and cutaneous MC responses are subject to the effects of environmental factors including ultraviolet radiation (UVR). Numerous studies have assessed the effects of UVR on MCs, in vitro and in vivo. Interestingly, UVR seems to have variable effects on non-activated and activated mast cells. In general, UV therapy is beneficial in the treatment of urticaria and mastocytosis, but the effects are variable depending on treatment regimen and type of UVR. Here, we review and summarise key reports from the older and current literature on the crosstalk of UVR and skin MCs. Specifically, we present the literature and discuss published reports on the effects of UVR on skin MCs in rodents and humans. In addition, we review the role of MCs in UVR-driven skin diseases and the influence of UV light on MC-mediated skin diseases. This summary of our current understanding of the interplay of skin MCs and UVR may help to improve the management of patients with urticaria and other MC disorders, to identify current gaps of knowledge, and to guide further research. K E Y W O R D Scancer, mast cell, ultraviolet radiation, urticaria

“…Schweintzger et al used mice homozygous for a different allele of Kit, Kit W‐Sh , to investigate the role of mast cells in inducing tolerance to UV‐mediated dermal hyperplasia and oedema. They found that deficiency of mast cells not only increased hyperplasia and oedema but also induced excessive scratching, a phenomenon that could be alleviated by grafting bone marrow‐derived cultured mast cells .…”

mentioning

confidence: 99%

Receptor tyrosine kinase Kit action in skin melanocytes: is it exclusively cell autonomous?

Hou

2015

Cellular functions are in a major way controlled by extracellular signals interacting with specific receptors whose stimulation leads to induction of distinct intracellular signalling cascades. KIT ligand (KITL, also known as stem cell or mast cell growth factor), for instance, is an extracellular ligand that specifically interacts with the receptor tyrosine kinase KIT expressed by a variety of cell types, not the least several cell types in the skin. Two recent articles in Experimental Dermatology describe studies in which Kit mutant mice have been used to address critical questions of the role of KIT in cutaneous mast cells in skin physiology and pathology (1,2 cells in inducing tolerance to UV-mediated dermal hyperplasia and oedema. They found that deficiency of mast cells not only increased hyperplasia and oedema but also induced excessive scratching, a phenomenon that could be alleviated by grafting bone marrow-derived cultured mast cells (2). Importantly, in both studies, the pathologies could be corrected by adoptive transfer of normal mast cells, alleviating the potential concern that in these genetic models, the respective pathologies might be due to the simultaneous absence of Kit in multiple cell types (for instance, also in immune cells). In a recent paper published in J Invest Dermatol, Aoki et al. (3) have addressed a similar question on the role of Kit but in a conceptually different way. They used a conditional (floxed) knock-in mouse in which Kit is specifically mutated in neural crest-derived melanocytes. It is well documented that suppression of Kit in the germline results in a reduction of melanocytes, leading to white patches of the coat or to total absence of melanocytes. While the total absence of KIT in homozygous Kit-null mice is associated with embryonic or postnatal lethality, mice heterozygous for a Kit-null mutation are viable and usually have only a minor white belly spot along with white paws and perhaps a white tail tip (4). So, what might the phenotypic consequences of a heterozygous or even homozygous lack of Kit specifically in melanocytes be?One might reason that the coat pigmentary phenotype may either be similar to that seen in equivalent germline mutations in Kit, suggesting that Kit acts exclusively cell autonomously, or be alleviated, suggesting that Kit wild-type, 'non-pigment' cells might somehow help Kit mutant melanocytes in their specification, migration, proliferation or differentiation. Surprisingly, Aoki et al. observed yet a third outcome: the pigmentary coat phenotype was worse than that observed with molecularly similar germline mutations in Kit. In fact, mice carrying one wild-type and one floxed Kit allele and also a transgene allowing expression of the CRE recombinase under the control of the tyrosinase promoter showed extensive, although variable, dorsal white spotting characterized by the absence of Dct-LacZ-labelled melanocytes. Such extensive dorsal spotting has not so far been seen in mice carrying the molecularly similar Kit W allele in the heterozygou...