CD4+ T-cell activation of bone marrow causes bone fragility and insulin resistance in type 2 diabetes

Cifuentes-Mendiola, Saúl Ernesto; Solís-Suarez, D.L.; Martínez‐Dávalos, A.; Godínez‐Victoria, Marycarmen; García‐Hernández, Ana Lilia

doi:10.1016/j.bone.2021.116292

Cited by 18 publications

(13 citation statements)

References 45 publications

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“… 39 Han et al 40 reported that CD4 T cells were markedly reduced in diabetic subjects among COVID-19 patients, and insulin resistance in T2DM can be caused by activating CD4 T-cells of bone marrow. 41 In addition, frequencies of CD4+ T cells were positively associated with age, BMI, HOMA2 estimate of β-cell function (HOMA2-B), and HOMA2 estimate of insulin resistance (HOMA2-IR). 42 Taken together, CD4 T cells are attractive targets for diagnosing and treating AS and T2DM.…”

Section: Discussionmentioning

confidence: 90%

Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes

Fu¹,

Xu²,

Zhang³

et al. 2023

JIR

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Background Atherosclerosis and type 2 diabetes mellitus contribute to a large part of cardiovascular events, but the underlying mechanism remains unclear. In this study, we focused on identifying the linking genes of the diagnostic biomarkers and effective therapeutic targets associated with these two diseases. Methods The transcriptomic datasets of atherosclerosis and type 2 diabetes mellitus were obtained from the GEO database. Differentially expressed genes analysis was performed by R studio software, and differential analysis including functional enrichment, therapeutic small molecular agents prediction, and protein–protein interaction analysis were applied to the common shared differentially expressed genes. Hub genes were identified and further validated using an independent dataset and clinical samples. Furthermore, we measured the expression correlations, immune cell infiltration, and diagnostic capability of the three key genes. Results We screened out 28 up-regulated and six down-regulated common shared differentially expressed genes. Functional enrichment analysis showed that cytokines and immune activation were involved in the development of these two diseases. Six small molecules with the highest absolute enrichment value were identified. Three critical genes (CD4, PLEK, and THY1) were further validated both in validation sets and clinical samples. The gene correlation analysis showed that CD4 was strongly positively correlated with PLEK, and ROC curves confirmed the good discriminatory capacity of CD4 and PLEK in two diseases. We have established the co-expression network between atherosclerosis lesions progressions and type 2 diabetes mellitus, and identified CD4 and PLEK as key genes in the two diseases, which may facilitate both development of diagnosis and therapeutic strategies.

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Section: Discussionmentioning

confidence: 90%

Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes

Fu¹,

Xu²,

Zhang³

et al. 2023

JIR

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show abstract

“…Currently, it is unclear whether T2DM can lead to the reduction of BMD. However, an increasing number of studies have shown that T2DM can increase bone fragility, 20,21 and such fragility leads to an increase in T2DM with OP. 22,23 The pathogenesis of T2DM complicated by OP is multifactorial and influenced by genetic and environmental factors.…”

Section: Discussionmentioning

confidence: 99%

The relationship between LRP5 rs556442 and rs638051 polymorphisms and mutations and their influence on bone metabolism in postmenopausal Xinjiang women with type 2 diabetes

Song¹,

Li²,

Liu³

et al. 2022

Adv Clin Exp Med

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“…La DT2 provoca un incremento en el porcentaje de linfocitos Th1 y Th17 y una disminución de las poblaciones Th2 y Treg en sangre periférica, médula ósea y tejido adiposo, lo que se correlaciona con el incremento en la concentración de INF-γ, TNF-α, IL-17 e IL-6 a nivel sistémico, el incremento de la resistencia a la insulina y la hiperglucemia 10,17,23,37,38 .…”

Section: Linfocitos T Cd4unclassified

“…La administración de CTLA4-Ig durante seis semanas en ratones con DT2 disminuyó la concentración de glucosa, la resistencia a la insulina, la inflamación sistémica y la inflamación en la médula ósea mejorando la salud ósea 38 ; además, en ratones con DT2 espontánea, la CTLA4-Ig redujo la resistencia a la insulina, los niveles de glucemia y mejoró el metabolismo de la glucosa mediante la disminución de la inflamación en el tejido adiposo 44 .…”

Section: Proteína De Fusión Ctla4-igunclassified

Papel fundamental de la inflamación sistémica de bajo grado en el desarrollo de la diabetes tipo 2

Cifuentes-Mendiola¹,

Velasquillo²,

García‐Hernández³

2022

ALAD

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CD4+ T-cell activation of bone marrow causes bone fragility and insulin resistance in type 2 diabetes

Cited by 18 publications

References 45 publications

Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes

Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes

The relationship between LRP5 rs556442 and rs638051 polymorphisms and mutations and their influence on bone metabolism in postmenopausal Xinjiang women with type 2 diabetes

Papel fundamental de la inflamación sistémica de bajo grado en el desarrollo de la diabetes tipo 2

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