PMID- 34360845
OWN - NLM
STAT- MEDLINE
DCOM- 20210908
LR  - 20210908
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 15
DP  - 2021 Jul 28
TI  - 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.
LID - 10.3390/ijms22158076 [doi]
LID - 8076
AB  - 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.
FAU - Conti, Pio
AU  - Conti P
AUID- ORCID: 0000-0002-9475-4924
AD  - Postgraduate Medical School, University of Chieti, 66100 Chieti, Italy.
FAU - Pregliasco, Fabrizio E
AU  - Pregliasco FE
AUID- ORCID: 0000-0002-3919-0679
AD  - Istituto Ortopedico Galeazzi, 20100 Milano, Italy.
FAU - Bellomo, Rosa G
AU  - Bellomo RG
AD  - Facolta di Scienze dell'Educazione Motoria, Universita "Carlo Bo", 61029 Urbino, 
      Italy.
FAU - Gallenga, Carla E
AU  - Gallenga CE
AUID- ORCID: 0000-0002-7426-8603
AD  - Department of Biomedical Sciences and Specialist Surgery, University of Ferrara, 
      44100 Ferrara, Italy.
FAU - Caraffa, Alessandro
AU  - Caraffa A
AD  - School of Pharmacy, University of Camerino, 62032 Camerino, Italy.
FAU - Kritas, Spyros K
AU  - Kritas SK
AD  - Department of Microbiology and Infectious Diseases, Aristotle University of 
      Thessaloniki, 54250 Macedonia, Greece.
FAU - Lauritano, Dorina
AU  - Lauritano D
AUID- ORCID: 0000-0002-3550-1812
AD  - Medicine and Surgery Centre of Neuroscience of Milan, University of 
      Milan-Bicocca, 20100 Milano, Italy.
FAU - Ronconi, Gianpaolo
AU  - Ronconi G
AD  - Clinica dei Pazienti del Territorio, Fondazione Policlinico Gemelli, 00168 Rome, 
      Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210728
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (IL-38 protein, human)
RN  - 0 (IL37 protein, human)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-33)
RN  - 0 (Interleukins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Inflammation
MH  - Interleukin 1 Receptor Antagonist Protein/therapeutic use
MH  - Interleukin-1/*immunology/therapeutic use
MH  - Interleukin-33/immunology
MH  - Interleukins/immunology/*therapeutic use
MH  - Mast Cells/immunology/metabolism
MH  - Psoriasis/drug therapy/*immunology
MH  - Skin
PMC - PMC8348737
OTO - NOTNLM
OT  - IL-1
OT  - IL-1Ra
OT  - IL-37
OT  - IL-38
OT  - cytokine
OT  - immunology
OT  - inflammation
OT  - mast cell
OT  - psoriasis
COIS- All the authors report no conflicts of interest relevant to this article.
EDAT- 2021/08/08 06:00
MHDA- 2021/09/09 06:00
PMCR- 2021/07/28
CRDT- 2021/08/07 01:08
PHST- 2021/06/24 00:00 [received]
PHST- 2021/07/22 00:00 [revised]
PHST- 2021/07/25 00:00 [accepted]
PHST- 2021/08/07 01:08 [entrez]
PHST- 2021/08/08 06:00 [pubmed]
PHST- 2021/09/09 06:00 [medline]
PHST- 2021/07/28 00:00 [pmc-release]
AID - ijms22158076 [pii]
AID - ijms-22-08076 [pii]
AID - 10.3390/ijms22158076 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jul 28;22(15):8076. doi: 10.3390/ijms22158076.