IL-34 Exerts Anti-Inflammatory Activities on Keratinocytes and Is Downregulated in Psoriatic-Inflamed Skin

Abstract

Interleukin-34 (IL-34) is expressed by keratinocytes in the skin and plays a role in Langerhans cell (LC) homeostasis through its binding to the colony-stimulating factor 1 receptor (CSF-1R) ( Greter et al., 2012 Greter M. Lelios I. Pelczar P. Hoeffel G. Price J. Leboeuf M. et al. Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. Immunity. 2012; 37: 1050-1060 Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar ; Wang et al., 2012 Wang Y. Szretter K.J. Vermi W. Gilfillan S. Rossini C. Cella M. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol. 2012; 13: 753-760 Crossref PubMed Scopus (652) Google Scholar ). In recent years, a growing body of literature has reported its overexpression during inflammation in tissues and/or in the serum of patients with rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases or Sjogren’s syndrome, in association with disease severity ( Munoz-Garcia et al., 2021 Munoz-Garcia J. Cochonneau D. Teletchea S. Moranton E. Lanoe D. Brion R. et al. The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis. Theranostics. 2021; 11: 1568-1593 Crossref PubMed Scopus (31) Google Scholar ). By contrast, some immunoregulatory properties of IL-34 have also been described in other physiopathological contexts, either by controlling the expression of proinflammatory cytokines or by promoting M2 macrophage differentiation and Treg cell functions ( Guillonneau et al., 2017 Guillonneau C. Bézie S. Anegon I. Immunoregulatory properties of the cytokine IL-34. Cell Mol Life Sci. 2017; 74: 2569-2586 Crossref PubMed Scopus (67) Google Scholar ). Although IL-34 is mainly produced in the skin, very few studies have investigated its expression, regulation and role during skin inflammation and it is still unclear whether IL-34 has a beneficial or a deleterious role. Li et al. reported low serum concentrations of IL-34 in psoriasis patients similar to those of healthy controls ( Li et al., 2017 Li J. Liu L. Rui W. Li X. Xuan D. Zheng S. et al. New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions. Dermatology. 2017; 233: 37-46 Crossref PubMed Scopus (67) Google Scholar ), without investigating IL-34 tissue expression. By contrast, Esaki et al. reported a reduced IL-34 expression in skin lesions of atopic dermatitis (AD) patients, suggesting that IL-34 could have immunoregulatory properties in the skin ( Esaki et al., 2015 Esaki H. Ewald D.A. Ungar B. Rozenblit M. Zheng X. Xu H. et al. Identification of novel immune and barrier genes in atopic dermatitis by means of laser capture microdissection. J Allergy Clin Immunol. 2015; 135: 153-163 Abstract Full Text Full Text PDF PubMed Google Scholar ).