The Potential Role of a Soluble γ-Chain Cytokine Receptor as a Regulator of IL-7-Induced Lymphoproliferative Disorders

Kim, Geona; Jo, Yuna; Lee, Byunghyuk; Ali, Laraib Amir; Lee, Bo-Ae; Hong, Changwan

doi:10.3390/ijms19113375

Cited by 2 publications

(2 citation statements)

References 33 publications

(58 reference statements)

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“…It is released by activated eosinophils and macrophages but also by endothelial and epithelial cells. Furthermore, it is implicated in diseases, such as atherosclerosis, in an independent manner from its action on eosinophils [34][35][36][37], as well as in CKD [38].…”

Section: Discussionmentioning

confidence: 99%

Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines

Perna

Russo

D’Esposito

et al. 2021

IJMS

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Vascular calcification (VC) is a risk factor for cardiovascular events and mortality in chronic kidney disease (CKD). Several components influence the occurrence of VC, among which inflammation. A novel uremic toxin, lanthionine, was shown to increase intracellular calcium in endothelial cells and may have a role in VC. A group of CKD patients was selected and divided into patients with a glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 and ≥45 mL/min/1.73 m2. Total Calcium Score (TCS), based on the Agatston score, was assessed as circulating lanthionine and a panel of different cytokines. A hemodialysis patient group was also considered. Lanthionine was elevated in CKD patients, and levels increased significantly in hemodialysis patients with respect to the two CKD groups; in addition, lanthionine increased along with the increase in TCS, starting from one up to three. Interleukin IL-6, IL-8, and Eotaxin were significantly increased in patients with GFR < 45 mL/min/1.73 m2 with respect to those with GFR ≥ 45 mL/min/1.73 m2. IL-1b, IL-7, IL-8, IL-12, Eotaxin, and VEGF increased in calcified patients with respect to the non-calcified. IL-8 and Eotaxin were elevated both in the low GFR group and in the calcified group. We propose that lanthionine, but also IL-8 and Eotaxin, in particular, are a key feature of VC of CKD, with possible marker significance.

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Section: Discussionmentioning

confidence: 99%

Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines

Perna

Russo

D’Esposito

et al. 2021

IJMS

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“…Although direct association analyses were not possible in STAT5 phosphorylation assays, we concluded that cytokine sensitivity of γ c high T-cell proportions promoted IL-2 (IL-15) rather than IL-7. Evidence for a role of differential γ c -dependent γ c cytokine signaling come from several animal models including experimental autoimmune encephalitis (EAE) and rheumatoid arthritis (25, 27, 32–34). Hong et al assessed implications of the sγ c chain on cytokine signaling and found that this inhibitory variant especially blocked IL-2R signaling probably by binding to the IL-2Rß chain and preventing the association with membrane γ c proteins (27).…”

Section: Discussionmentioning

confidence: 99%

CD4+ T-Cells With High Common γ Chain Expression and Disturbed Cytokine Production Are Enriched in Children With Type-1 Diabetes

et al. 2019

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The common gamma chain (γ c ) contributes to the formation of different cytokine receptors [e.g., IL-2 receptor (IL-2R), IL-7R, and IL-15R], which are important for generation of self-reactive T-cells in autoimmune diseases, like in type 1 diabetes (T1D). Whereas, the roles of membrane and soluble IL-2Rα and IL-7Rα variants in T1D disease pathogenesis are well-described, effects of γ c expression and availability for dependent receptors remain elusive. We investigated expression of the γ c and dependent receptors on T-cells and soluble γ c concentrations in serum from patients with T1D ( n = 34) and healthy controls ( n = 27). Effector T-cell cytokines as well as IL-2, IL-7, and IL-15 induced STAT5 phosphorylation were analyzed to determine functional implications of differential γ c expression of CD4 + T-cell subsets classified by t-distributed Stochastic Neighbor Embedding (t-SNE) analyses. We found increased γ c and IL-7Rα expression of CD4 + T-cells from T1D patients as compared to controls. t-SNE analyses assigned differential expression to subsets of memory T-cells co-expressing γ c and IL-7Rα. Whereas, γ c expression was positively correlated with IL-2Rα in memory T-cells from healthy controls, no dependency was found for patients with T1D. Similarly, the effector T-cell cytokine, IL-21, correlated inversely with γ c expression in healthy controls, but not in T1D patients. Finally, T1D patients with high γ c expression had increased proportions of IL-2 sensitive pSTAT5 + effector T-cells. These results indicated aberrantly high γ c expression of T-cells from T1D patients with implications on dependent cytokine receptor signaling and effector T-cell cytokine production.

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The Potential Role of a Soluble γ-Chain Cytokine Receptor as a Regulator of IL-7-Induced Lymphoproliferative Disorders

Cited by 2 publications

References 33 publications

Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines

Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines

CD4+ T-Cells With High Common γ Chain Expression and Disturbed Cytokine Production Are Enriched in Children With Type-1 Diabetes

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