Integrated metabolomic analysis and cytokine profiling define clusters of immuno-metabolic correlation in new-onset psoriasis

Abstract

The association between the metabolic profile and inflammatory cytokines in psoriasis is poorly understood. We analyzed the metabolic and cytokine/chemokine profiles in serum and skin from patients with new-onset psoriasis and healthy subjects (n = 7/group) by HR-MAS NMR and Bio-Plex immunoassay. Immuno-metabolic correlation matrix was analyzed in skin and serum to identify a potential immune-metabolic signature. Metabolomics analysis showed a significant increase in ascorbate and a decrease in scyllo-inositol, and a trend towards an increase in eight other metabolites in psoriatic skin. In serum, there was a significant increase of dimethylglycine and isoleucine. In parallel, psoriatic skin exhibited an increase of early inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1β) and correlation analysis highlighted some major clusters of immune-metabolic correlations. A cluster comprising scyllo-inositol and lysine showed correlations with T-cell cytokines; a cluster comprising serine and taurine showed a negative correlation with early inflammatory cytokines (IL-6, G-CSF, CCL3). A strong positive correlation was enlightened between glutathione and inflammatory cytokines/angiogenesis promoters of psoriasis. The integration of metabolic and immune data indicated a molecular signature constituted by IL-6, IL1-ra, DMG, CCL4, Ile, Gly and IL-8, which could discriminate patients and healthy subjects and could represent a candidate tool in the diagnosis of new-onset psoriasis.

Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma

“…In particular, simultaneous blockade of IL-4Ra, a common part of the receptor complex of IL-4 and IL-13, with Dupilumab showed significant therapeutic effect and is approved for patients with severe eosinophilic asthma [ 8 , 9 ], despite poor efficacy of single anti-IL-4 and anti-IL-13 therapeutics [ 58 , 59 , 60 , 61 ]. Under inflammatory conditions TNF and IL-6 demonstrate some functional redundancy: for example, they both mediate inflammatory response during sepsis [ 62 ], and may act as immunometabolic transmitters [ 63 , 64 , 65 ]. On the other hand, due to distinct intracellular signaling of their cognate receptors, these cytokines may exhibit distinct functions or work synergistically to promote inflammation [ 66 , 67 , 68 , 69 ].…”

A systematic review: metabolomics‐based identification of altered metabolites and pathways in the skin caused by internal and external factors

“…53 Psoriasis is not associated with DNA damage, and no changes in both metabolisms were observed. 54,[56][57][58][59][60] Similarly, metabolic studies of basal cell carcinoma cells showed no changes in this metabolic pathway. 55…”

“…54,58 However, the study by Tarentini et al (2021) reports that lactate level was increased in biopsies of psoriasis-affected skin. 60…”

“…Metabolic alteration in psoriatic skin was described in five studies. 54,[56][57][58]60 In addition, two studies addressed the metabolic alteration caused by atopic dermatitis (AD) 59 and basal cell carcinoma 55 respectively.…”

“…Psoriasis seemed to be associated with upregulated glucose metabolism caused by the increased efficiency of pyruvate dehydrogenase and reduced lactate synthesis. 54,58 However, the study by Tarentini et al (2021) reports that lactate level was increased in biopsies of psoriasis-affected skin. 60…”