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

IL-34 is expressed by keratinocytes (KCs) in the skin and plays a role in the homeostasis of Langerhans cells by its binding to the colony-stimulating factor 1 receptor ( 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 (431) 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 (672) 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 syndrome, in association with disease severity ( Muñoz-Garcia et al., 2021 Muñoz-Garcia J. Cochonneau D. Télétchéa 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 (45) Google Scholar ). In 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 regulatory T-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 (71) 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., 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 (71) Google Scholar reported low serum concentrations of IL-34 in patients with psoriasis to be similar to those in healthy controls without investigating IL-34 tissue expression. In contrast, 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 Scopus (160) Google Scholar reported a reduced IL-34 expression in skin lesions of patients with atopic dermatitis, suggesting that IL-34 could have immunoregulatory properties in the skin.