Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Voß, Martin; Kotrba, Johanna; Gaffal, Evelyn; Katsoulis‐Dimitriou, Konstantinos; Dudeck, Anne

doi:10.3390/ijms22094589

Cited by 53 publications

(64 citation statements)

References 349 publications

(429 reference statements)

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“…They can produce a large array of mediators and respond to perturbations in their environment, leading to their involvement in several inflammatory disorders ( 11 , 12 ). Whilst the role of mast cells in acne is poorly understood, these cells are known to play important roles in the skin immune system ( 13 ). Furthermore, different resident and recirculating T cell subsets are also known to participate in immune surveillance of the skin ( 14 ) and might be involved in the initiation of the immune response in acne.…”

Section: Introductionmentioning

confidence: 99%

IL-17+ Mast Cell/T Helper Cell Axis in the Early Stages of Acne

et al. 2021

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Acne is a multifactorial disease driven by physiological changes occurring during puberty in the pilosebaceous unit (PSU) that leads to sebum overproduction and a dysbiosis involving notably Cutibacterium acnes. These changes in the PSU microenvironment lead to a shift from a homeostatic to an inflammatory state. Indeed, immunohistochemical analyses have revealed that inflammation and lymphocyte infiltration can be detected even in the infraclinical acneic stages, highlighting the importance of the early stages of the disease. In this study, we utilized a robust multi-pronged approach that included flow cytometry, confocal microscopy, and bioinformatics to comprehensively characterize the evolution of the infiltrating and resident immune cell populations in acneic lesions, beginning in the early stages of their development. Using a discovery cohort of 15 patients, we demonstrated that the composition of immune cell infiltrate is highly dynamic in nature, with the relative abundance of different cell types changing significantly as a function of clinical lesion stage. Within the stages examined, we identified a large population of CD69+ CD4+ T cells, several populations of activated antigen presenting cells, and activated mast cells producing IL-17. IL-17+ mast cells were preferentially located in CD4+ T cell rich areas and we showed that activated CD4+ T cells license mast cells to produce IL-17. Our study reveals that mast cells are the main IL-17 producers in the early stage of acne, underlying the importance of targeting the IL-17+ mast cell/T helper cell axis in therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

IL-17+ Mast Cell/T Helper Cell Axis in the Early Stages of Acne

et al. 2021

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“…As expected, ILC2 cells were clearly increased in CRE- or OVA-treated mice relative to those untreated mice ( Figure 2B ), while the increase did not reach statistical significance for CRE treatment because of the limited sample size ( P = 0.071). Studies have also provided evidence that mast cells were increased in skin lesions of patients with AD ( 32 , 33 ) and have suggested that mast cells may participate in maintaining barrier function and homeostasis ( 30 , 36 , 37 ). Thus, we specifically analyzed mast cells (CD45 + CD3 – FcεRI + cKit + cells) in the skin isolated from those CRE- or OVA-treated mice ( Figure 2C ).…”

Section: Resultsmentioning

confidence: 99%

“…Mast cells are known to be critical in the regulation of allergic diseases because of their preferential localization close to skin epidermis or at the site of the tissue mucosa where exposure to environmental antigens and chemicals often occurs ( 26 – 30 ). Mast cells have large numbers of granules, containing mediators like histamine, serotonin, proteases, and cytokines, and they can synthesize prostaglandins, leukotrienes, and cytokines, thereby initiating inflammatory immune responses ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

Dendritic cell immunoreceptor drives atopic dermatitis by modulating oxidized CaMKII-involved mast cell activation

Luo¹,

Chen²,

Yang³

et al. 2022

JCI Insight

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Allergens have been identified as potential triggers in patients with atopic dermatitis (AD). Patients with AD are highly sensitive to cockroach allergen. The underlying mechanism, however, remains undetermined. Here, we established a cockroach allergen–induced AD-like mouse model, and we demonstrate that repeated exposure to cockroach allergen led to aggravated mouse skin inflammation, characterized by increased type 2 immunity, type 2 innate lymphoid cells (ILC2s), and mast cells. Increased mast cells were also observed in patients with AD. Mast cell–deficient mice ( Kit W-sh/W-sh ) showed diminished skin inflammation, suggesting that mast cells are required in allergen-induced skin inflammation. Furthermore, DC immunoreceptor (DCIR) is upregulated in skin mast cells of patients with AD and mediates allergen binding and uptake. DCIR –/– mice or reconstituted Kit W-sh/W-sh mice with DCIR –/– mast cells showed a significant reduction in AD-like inflammation. Both in vitro and in vivo analyses demonstrate that DCIR –/– mast cells had reduced IgE-mediated mast cell activation and passive cutaneous anaphylaxis. Mechanistically, DCIR regulates allergen-induced IgE-mediated mast cell ROS generation and oxidation of calmodulin kinase II (ox-CaMKII). ROS-resistant CaMKII (MM-VV δ ) prevents allergen-induced mast cell activation and inflammatory mediator release. Our study reveals a DCIR/ROS/CaMKII axis that controls allergen-induced mast cell activation and AD-like inflammation.

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“…Several studies have been performed to elucidate the roles of MCs in the skin under steady and diseased conditions. MCs play both facilitating and regulatory roles in a context-dependent manner ( 9 – 13 ). So far, the interleukin (IL)-10-mediated mechanisms have mostly been investigated as the regulatory mechanisms of MCs.…”

Section: Introductionmentioning

confidence: 99%

Novel Insights Into the Immune-Regulatory Functions of Mast Cells in the Cutaneous Immune Response

Honda

Keith

2022

Front. Immunol.

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Skin is a frontline organ that is continuously exposed to external stimuli, including pathogens. Various immune cells reside in the skin under physiological conditions and protect the body from the entry of pathogens/antigens by interacting with each other and orchestrating diverse cutaneous immune responses. To avoid unnecessary inflammation and tissue damage during the elimination of external pathogens and antigens, skin possesses regulatory systems that fine-tune these immune reactions. Mast cells (MCs) are one of the skin-resident immune cell populations that play both effector and regulatory functions in the cutaneous immune response. So far, the interleukin-10-mediated mechanisms have mostly been investigated as the regulatory mechanisms of MCs. Recent studies have elucidated other regulatory mechanisms of MCs, such as the maintenance of regulatory T/B cells and the programmed cell death protein-1/programmed cell death-ligand 1-mediated inhibitory pathway. These regulatory pathways of MCs have been suggested to play important roles in limiting the excessive inflammation in inflammatory skin diseases, such as contact and atopic dermatitis. The regulatory functions of MCs may also be involved in the escape mechanisms of antitumor responses in skin cancers, such as melanoma. Understanding and controlling the regulatory functions of skin MCs may lead to novel therapeutic strategies for inflammatory skin diseases and skin cancers.

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Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Cited by 53 publications

References 349 publications

IL-17+ Mast Cell/T Helper Cell Axis in the Early Stages of Acne

IL-17+ Mast Cell/T Helper Cell Axis in the Early Stages of Acne

Dendritic cell immunoreceptor drives atopic dermatitis by modulating oxidized CaMKII-involved mast cell activation

Novel Insights Into the Immune-Regulatory Functions of Mast Cells in the Cutaneous Immune Response

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