Keratinocyte-derived S100A9 modulates neutrophil infiltration and affects psoriasis-like skin and joint disease

Mellor LF, Gago-Lopez N, Bakiri L, Schmidt FN, Busse B, Rauber S, Jimenez M, Megias D, Oterino-Soto S, Sanchez-Prieto R, Grivennikov S, Pu X, Oxford J, Ramming A, Schett G, Wagner EF (2022)


Publication Type: Journal article

Publication year: 2022

Journal

DOI: 10.1136/annrheumdis-2022-222229

Abstract

Objectives S100A9, an alarmin that can form calprotectin (CP) heterodimers with S100A8, is mainly produced by keratinocytes and innate immune cells. The contribution of keratinocyte-derived S100A9 to psoriasis (Ps) and psoriatic arthritis (PsA) was evaluated using mouse models, and the potential usefulness of S100A9 as a Ps/PsA biomarker was assessed in patient samples. Methods Conditional S100A9 mice were crossed with DKO* mice, an established psoriasis-like mouse model based on inducible epidermal deletion of c-Jun and JunB to achieve additional epidermal deletion of S100A9 (TKO* mice). Psoriatic skin and joint disease were evaluated in DKO* and TKO* by histology, microCT, RNA and proteomic analyses. Furthermore, S100A9 expression was analysed in skin, serum and synovial fluid samples of patients with Ps and PsA. Results Compared with DKO* littermates, TKO* mice displayed enhanced skin disease severity, PsA incidence and neutrophil infiltration. Altered epidermal expression of selective pro-inflammatory genes and pathways, increased epidermal phosphorylation of STAT3 and higher circulating TNF alpha were observed in TKO* mice. In humans, synovial S100A9 levels were higher than the respective serum levels. Importantly, patients with PsA had significantly higher serum concentrations of S100A9, CP, VEGF, IL-6 and TNF alpha compared with patients with only Ps, but only S100A9 and CP could efficiently discriminate healthy individuals, patients with Ps and patients with PsA. Conclusions Keratinocyte-derived S100A9 plays a regulatory role in psoriatic skin and joint disease. In humans, S100A9/CP is a promising marker that could help in identifying patients with Ps at risk of developing PsA.

Authors with CRIS profile

Involved external institutions

How to cite

APA:

Mellor, L.F., Gago-Lopez, N., Bakiri, L., Schmidt, F.N., Busse, B., Rauber, S.,... Wagner, E.F. (2022). Keratinocyte-derived S100A9 modulates neutrophil infiltration and affects psoriasis-like skin and joint disease. Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2022-222229

MLA:

Mellor, Liliana F., et al. "Keratinocyte-derived S100A9 modulates neutrophil infiltration and affects psoriasis-like skin and joint disease." Annals of the Rheumatic Diseases (2022).

BibTeX: Download