IL-36 Cytokines: Regulators of Inflammatory Responses and Their Emerging Role in Immunology of Reproduction

GND
121666272X
ORCID
0000-0003-4093-1419
Affiliation
Placenta Lab, Department of Obstetrics, Jena University Hospital
Murrieta-Coxca, José Martin;
ORCID
0000-0001-5063-3525
Affiliation
Departamento de Inmunología, Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, 11340 Mexico City, Mexico,
Rodríguez-Martínez, Sandra;
Affiliation
Departamento de Inmunología, Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, 11340 Mexico City, Mexico,
Cancino-Diaz, Mario Eugenio;
GND
113616759
ORCID
0000-0001-5299-595X
Affiliation
Placenta Lab, Department of Obstetrics, Jena University Hospital, 07740 Jena, Germany,
Markert, Udo R.;
GND
1216422818
ORCID
0000-0002-2889-5921
Affiliation
Placenta Lab, Department of Obstetrics, Jena University Hospital
Favaro, Rodolfo R.;
GND
1029632839
ORCID
0000-0002-7348-059X
Affiliation
Placenta Lab, Department of Obstetrics, Jena University Hospital, 07740 Jena, Germany,
Morales-Prieto, Diana M.

The IL-36 subfamily of cytokines has been recently described as part of the IL-1 superfamily. It comprises three pro-inflammatory agonists (IL-36α, IL-36β, and IL-36γ), their receptor (IL-36R), and one antagonist (IL-36Ra). Although expressed in a variety of cells, the biological relevance of IL-36 cytokines is most evident in the communication between epithelial cells, dendritic cells, and neutrophils, which constitute the common triad responsible for the initiation, maintenance, and expansion of inflammation. The immunological role of IL-36 cytokines was initially described in studies of psoriasis, but novel evidence demonstrates their involvement in further immune and inflammatory processes in physiological and pathological situations. Preliminary studies have reported a dynamic expression of IL-36 cytokines in the female reproductive tract throughout the menstrual cycle, as well as their association with the production of immune mediators and cellular recruitment in the vaginal microenvironment contributing to host defense. In pregnancy, alteration of the placental IL-36 axis has been reported upon infection and pre-eclampsia suggesting its pivotal role in the regulation of maternal immune responses. In this review, we summarize current knowledge regarding the regulatory mechanisms and biological actions of IL-36 cytokines, their participation in different inflammatory conditions, and the emerging data on their potential role in normal and complicated pregnancies.

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