Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra

Pio Conti
* ORCID logo ,
Fabrizio Pregliasco
ORCID logo ,
Rosa G. Bellomo
,
Carla E. Gallenga
ORCID logo ,
Alessandro Caraffa
,
Spyros K. Kritas
,
Dorina Lauritano
ORCID logo ,
Gianpaolo Ronconi
Version 1 : Received: 24 January 2021 / Approved: 25 January 2021 / Online: 25 January 2021 (15:57:19 CET)

How to cite: Conti, P.; Pregliasco, F.; Bellomo, R.G.; Gallenga, C.E.; Caraffa, A.; Kritas, S.K.; Lauritano, D.; Ronconi, G. Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra. Preprints 2021, 2021010520. https://doi.org/10.20944/preprints202101.0520.v1 Conti, P.; Pregliasco, F.; Bellomo, R.G.; Gallenga, C.E.; Caraffa, A.; Kritas, S.K.; Lauritano, D.; Ronconi, G. Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra. Preprints 2021, 2021010520. https://doi.org/10.20944/preprints202101.0520.v1

Abstract

Psoriasis (PS) is an autoimmune skin disease mediated by immune cells that typically presents inflammatory erythematous plaques, and it 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 pro-inflammatory cytokines and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophage to release IL-36, a powerful pro-inflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic pro-inflammatory diseases such as psoriasis. Suppressing IL-36 results in a noticeable improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra which binds on to IL-36 receptor ligand, but suppression can also occur by binding IL-38 to the IL-36R receptor. 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 pro-inflammatory IL-36 inhibited by IL-38. In this article we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis and hold promise of an innovative therapeutic tool.

Keywords

mast cell; psoriasis; inflammation; cytokine; Il-37; IL-38; IL-1Ra

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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