Activation of mast cells mediates inflammatory response in psoriasis: Potential new therapeutic approach with IL‐37

Conti, Pio; Gallenga, Carla Enrica; Ronconi, Gianpaolo; Caraffa, Alessandro; Kritas, S K

doi:10.1111/dth.12943

Cited by 19 publications

(22 citation statements)

References 42 publications

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“…Psoriasis is considered to be an autoimmune disorder that is characterized by massive immune cell infiltration into the dermis and epidermis, followed by an abnormal proliferation of KCs [ 308 ]. The skin disease is perpetuated by both innate and adaptive mechanisms ( Figure 4 A) and, although the inflammation appears locally in the skin, it involves detrimental effects on patient quality of life and may be even accompanied by systemic manifestations [ 309 ].…”

Section: Mast Cell Contribution To Inflammatory Skin Disordersmentioning

confidence: 99%

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

Voß

Kotrba

Gaffal

et al. 2021

IJMS

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Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

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Section: Mast Cell Contribution To Inflammatory Skin Disordersmentioning

confidence: 99%

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

Voß

Kotrba

Gaffal

et al. 2021

IJMS

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“…MCs play pivotal roles in the development of various types of diseases. For example, MCs are crucial cells not only in allergic responses, atopic dermatitis, allergic rhinitis, and bronchial asthma but also in other non-allergic diseases, including psoriasis, 25 wound healing, 7 ulcerative colitis, 26 and alopecia areata. 23 Furthermore, MCs are involved in the pathogenesis of different kinds of neoplasms.…”

Section: Discussionmentioning

confidence: 99%

The Mast Cell–SCF–CB1 Interaction Is a Key Player in Seborrheic Keratosis

Yamanaka‐Takaichi

Sugawara

Sumitomo

et al. 2020

J Histochem Cytochem.

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Mast cell (MC) is an important player in the development of skin diseases, including atopic dermatitis, psoriasis, and urticaria. It is reported that MC infiltration and activation are observed around various types of tumors and speculated that MCs play key roles in their pathogenesis. As MCs in human seborrheic keratosis (SK) have not been well investigated, here we focused on the MCs in SK. The number of c-Kit and tryptase-positive MCs was significantly increased around the SK compared with the marginal lesion. Degranulated MCs were also increased around the tumors. Furthermore, MC growth factor, stem cell factor (SCF), expression within the SK was significantly upregulated compared with the marginal lesion. Interestingly, one of the cognitive regulators of SCF expression, cannabinoid receptor type 1 (CB1) immunoreactivity was downregulated within the SK. Our results suggest that MCs play important roles in the pathogenesis of SK and that SCF can be also deeply involved in the development of SKs. Our current results highlight the CB1–SCF–MC interaction as a novel mechanism of SK development and this also will be utilized for developing a novel treatment.

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“…MCs can be recruited into inflamed skin by diverse chemotactic molecules (including Vascular endothelial growth factor (VEGF), stem cell factor (SCF), and a number of CC and CXC chemokines) produced by immune cells [ 27 ]. MCs have been proposed to influence many biological processes, including autoimmune disorders [ 28 ].…”

Section: Description and Function Of Mast Cells (Mcs)mentioning

confidence: 99%

Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra

Conti

Pregliasco

Fulle

et al. 2021

IJMS

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Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36—a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs—a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

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Activation of mast cells mediates inflammatory response in psoriasis: Potential new therapeutic approach with IL‐37

Cited by 19 publications

References 42 publications

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

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

The Mast Cell–SCF–CB1 Interaction Is a Key Player in Seborrheic Keratosis

Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra

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