2D Visualization of the Psoriasis Transcriptome Fails to Support the Existence of Dual-Secreting IL-17A/IL-22 Th17 T Cells
FRONTIERS IN IMMUNOLOGY
Authors: Le, Stephanie T.; Merleev, Alexander A.; Luxardi, Guillaume; Shimoda, Michiko; Adamopoulos, Lannis E.; Tsoi, Lam C.; Wang, Jenny Z.; Alexanian, Claire; Raychaudhuri, Siba P.; Hwang, Samuel T.; Gudjonsson, Johann; Marusina, Alina, I; Maverakis, Emanual
Abstract
The present paradigm of psoriasis pathogenesis revolves around the IL-23/IL-17A axis. Dual-secreting Th17 T cells presumably are the predominant sources of the psoriasis phenotype-driving cytokines, IL-17A and IL-22. We thus conducted a meta-analysis of independently acquired RNA-seq psoriasis datasets to explore the relationship between the expression of 1L17A and IL22. This analysis failed to support the existence of dual secreting IL-17A/IL-22 Th17 cells as a major source of these cytokines. However, variable relationships amongst the expression of psoriasis susceptibility genes and of IL17A, IL22, and IL23A were identified. Additionally, to shed light on gene expression relationships in psoriasis, we applied a machine learning nonlinear dimensionality reduction strategy (t-SNE) to display the entire psoriasis transcriptome as a 2-dimensonal image. This analysis revealed a variety of gene clusters, relevant to psoriasis pathophysiology but failed to support a relationship between IL17A and IL22. These results support existing theories on alternative sources of IL-17A and IL-22 in psoriasis such as a Th22 cells and non-T cell populations.
Artocarpus tonkinensis Protects Mice Against Collagen-Induced Arthritis and Decreases Th17 Cell Function
FRONTIERS IN PHARMACOLOGY
Authors: Adorisio, Sabrina; Fierabracci, Alessandra; Muscari, Isabella; Liberati, Anna Marina; Calvitti, Mario; Cossignani, Lina; Blasi, Francesca; Tran Duc Quan; Nguyen Thanh Tam; Tran Van Sung; Riccardi, Carlo; Trinh Thi Thuy; Delfino, Domenico V.
Abstract
Artocarpus tonkinensis (Moraceae) is a tree that grows in north Vietnam whose leaf decoction is used as a traditional remedy by the Hmong ethnic group to treat arthritis and backache. Our study evaluated the decoction's efficacy and mechanism of action in DBA/ 1J mice with collagen-induced arthritis (CIA). Mice treated with the decoction (At) either from the first collagen immunization or after CIA development experienced significantly less joint edema and inflammatory infiltration, whereas CIA-induced cartilage damage could only be prevented by early At treatment. Autoimmune gene expression profiles showed that Th17 cell-associated chemokine CCL20 and cytokines IL-6, IL17, and IL-22 were strongly downregulated by At. Reduced expression of IL-2, IL-17, IL-22, and FasL in lymph node cells from At-treated mice was further confirmed by real-time PCR. The decoction also inhibited polarization of Th17 cells from CD4 C splenic T cells according to levels of IL-17 and RORC, a Th17 cell-specific transcription factor. Chromatographic analysis identified At's major component as maesopsin-beta-D- glucoside, which could inhibit in vitro differentiation of Th17 cells. The decoction significantly alleviated the signs and symptoms of CIA and inhibited the development and function of Th17 cells, highlighting its potent anti-inflammatory activity.