<i>Ahnak</i>-knockout mice show susceptibility to<i>Bartonella henselae</i>infection because of CD4+ T cell inactivation and decreased cytokine secretion

Choi, Eung‐Chil; Lee, Hee Woo; Lee, Jun Sik; Kim, Il Yong; Shin, Jae Hoon; Seong, Je Kyung

doi:10.5483/bmbrep.2019.52.4.310

Cited by 14 publications

(17 citation statements)

References 22 publications

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“…In addition, because whole-body Ahnak KO mice were used in our study, it should be considered that decreased inflammatory signaling in Ahnak KO mice may result in attenuated lipid accumulation. This has been strongly supported by an earlier observation that Ahnak KO mice showed CD4 + T cell inactivation and decreased cytokine secretion 50 . Thus, attenuated lipid accumulation in the liver of Ahnak KO mice fed a HFD may result in the downregulation of inflammatory signaling.…”

Section: Discussionsupporting

confidence: 72%

Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

et al. 2021

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The AHNAK nucleoprotein has been determined to exert an anti-obesity effect in adipose tissue and further inhibit adipogenic differentiation. In this study, we examined the role of AHNAK in regulating hepatic lipid metabolism to prevent diet-induced fatty liver. Ahnak KO mice have reportedly exhibited reduced fat accumulation in the liver and decreased serum triglyceride (TG) levels when provided with either a normal chow diet or a high-fat diet (HFD). Gene expression profiling was used to identify novel factors that could be modulated by genetic manipulation of the Ahnak gene. The results revealed that fibroblast growth factor 21 (FGF21) was markedly increased in the livers of Ahnak KO mice compared with WT mice fed a HFD. Ahnak knockdown in hepatocytes reportedly prevented excessive lipid accumulation induced by palmitate treatment and was associated with increased secretion of FGF21 and the expression of genes involved in fatty acid oxidation, which are primarily downstream of PPARα. These results indicate that pronounced obesity and hepatic steatosis are attenuated in HFD-fed Ahnak KO mice. This may be attributed, in part, to the induction of FGF21 and regulation of lipid metabolism, which are considered to be involved in increased fatty acid oxidation and reduced lipogenesis in the liver. These findings suggest that targeting AHNAK may have beneficial implications in preventing or treating hepatic steatosis.

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Section: Discussionsupporting

confidence: 72%

Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

et al. 2021

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“…The mass spectrometry analysis identified 24 proteins, including Ahnak, that potentially interacted with Gm40600 (Figure 6c, see Supplementary material, Table ). Ahnak was our protein of interest, because Ahnak KO mice have an impairment in Th1 and Th2 immunity and IFN‐γ and IL‐4 secretion [29]. The co‐IP and Western blot further proved that Ahnak interacted with Gm40600 (Figure 6d).…”

Section: Resultsmentioning

confidence: 98%

“…Altogether, these results suggest that Gm40600 promotes CD4 + T‐cell activation by up‐regulating the Ahnak‐mediated calcium signalling pathway. A recent study demonstrated that Ahnak knockout mice had an impairment of Th1 and Th2 immunity and IFN‐γ and IL‐4 secretion [29]. In addition, calcium signalling‐activated NFAT proteins are involved in the function of lineage‐specific transcription factors during the differentiation of Th1, Th2, Th17 [37, 38] and Tfh [39].…”

Section: Discussionmentioning

confidence: 99%

“…Ahnak, a large scaffold protein, is reported to be required for calcium signalling during CD4 + T‐cell activation [5, 6]. Importantly, the knockout (KO) of Ahnak inactivates CD4 + T‐cell responses and impairs IFN‐γ and IL‐4 secretion [7]. In addition, Ahnak KO causes 50% reduction in Cav1.1α1 membrane protein expression in T‐cell receptor (TCR)‐stimulated CD4 + T cells [5, 7].…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, the knockout (KO) of Ahnak inactivates CD4 + T‐cell responses and impairs IFN‐γ and IL‐4 secretion [7]. In addition, Ahnak KO causes 50% reduction in Cav1.1α1 membrane protein expression in T‐cell receptor (TCR)‐stimulated CD4 + T cells [5, 7]. Thus, Ahnak plays an essential role in Ca2+ signalling‐mediated CD4 + T‐cell activation.…”

Section: Introductionmentioning

confidence: 99%

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Gm40600 promotes CD4⁺ T‐cell responses by interacting with Ahnak

Fang

Zhai

et al. 2021

Immunology

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It is important to characterize novel proteins involved in T‐ and B‐cell responses. Our previous study demonstrated that a novel protein, Mus musculus Gm40600, reduced the proliferation of Mus musculus plasmablast (PB)‐like SP 2/0 cells and B‐cell responses induced in vitro by LPS. In the present study, we revealed that Gm40600 directly promoted CD4+ T‐cell responses to indirectly up‐regulate B‐cell responses. Importantly, we found that CD4+ T‐cell responses, including T‐cell activation and differentiation and cytokine production, were increased in Gm40600 transgenic (Tg) mice and were reduced in Gm40600 knockout (KO) mice. Finally, we demonstrated that Gm40600 promoted the Ahnak‐mediated calcium signalling pathway by interacting with Ahnak to maintain a cytoplasmic lateral location of Ahnak in CD4+ T cells. Collectively, our data suggest that Gm40600 promotes CD4+ T‐cell activation to up‐regulate the B‐cell response via interacting with Ahnak to promote the calcium signalling pathway. The results suggest that targeting Gm40600 may be a means to control CD4+ T‐cell‐related diseases.

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Identification of Immune-Linked Hub Genes and Diagnostic Model Construction in Schizophrenia

et al. 2023

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Schizophrenia (SCZ) is a prevalent, severe, and persistent mental disorder with an unknown etiology. Growing evidence indicates that immunological dysfunction is vital in the development of SCZ. Our study aims to uncover potential immune-linked hub genes and immune infiltration characteristics of SCZ, as well as to develop a diagnostic model based on immune-linked central genes. GSE38484 and GSE54913 chip expression data for patients with SCZ and healthy controls were retrieved. Weighted gene co-expression network analysis (WGCNA) was performed to identify major module genes and critical immune-linked genes. Functional enrichment analysis was conducted to elucidate the involvement of key genes in the immunological response to SCZ, along with the examination of their protein interactions. Moreover, 202 peripheral blood samples were examined using the single-sample gene set enrichment analysis (ssGSEA) method to detect distinct immune cell types. Hub immune-linked genes in SCZ were identified using the minimal absolute contraction and selection operator analysis. Receptor profiles of central immune-linked genes were analyzed to distinguish the two groups. Finally, the association between immune-linked hub genes and various types of immune cells was assessed. Our findings revealed ten immune cell types and nine key genes involved in SCZ, including effector memory CD4+ T cells, activated CD8+ T cells, mast cells, naive CD8+ T cells, PBMC, type 17 helper cells (Th17), central memory CD8+ T cells, CD56 bright NK cells, memory B cells, and regulatory T cells. Diagnostic models constructed using LASSO regression exhibited an average area under the curve (AUC) of 0.866. Our results indicate immunological dysfunction as a factor in the development of SCZ. ASGR2, ADRM1, AHANK, S100A8, FUCA1, AKNA, GATA3, AHCYL2, and PTRH2 are the key regulatory genes of immune cells, highlighting their potential as novel therapeutic targets for SCZ.

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Ahnak-knockout mice show susceptibility toBartonella henselaeinfection because of CD4+ T cell inactivation and decreased cytokine secretion

Cited by 14 publications

References 22 publications

Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

Gm40600 promotes CD4⁺ T‐cell responses by interacting with Ahnak

Identification of Immune-Linked Hub Genes and Diagnostic Model Construction in Schizophrenia

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Ahnak-knockout mice show susceptibility toBartonella henselaeinfection because of CD4+ T cell inactivation and decreased cytokine secretion

Cited by 14 publications

References 22 publications

Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

Gm40600 promotes CD4+ T‐cell responses by interacting with Ahnak

Identification of Immune-Linked Hub Genes and Diagnostic Model Construction in Schizophrenia

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Gm40600 promotes CD4⁺ T‐cell responses by interacting with Ahnak