LKB1 restrains dendritic cell function

Wculek, Stefanie K.; Sancho, David

doi:10.1038/s41422-019-0169-0

Cited by 6 publications

(9 citation statements)

References 12 publications

(54 reference statements)

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“…The dysregulation of IL-17A and IFN-γ in adipose tissue might be one of the critical contributors. Moreover, loss of Lkb1 in CD11c + cells remarkably increases splenic T cell responses under HFD exposure, which is consistent with other reported evidence on CD11c Cre Lkb1 f/f mice [ 26 – 28 , 47 ]. It is reported that activation of autoreactive T cells is one of critical contributors in autoimmune destruction of beta cells [ 65 ].…”

Section: Discussionsupporting

confidence: 92%

Loss of Lkb1 in CD11c+ myeloid cells protects mice from diet-induced obesity while enhancing glucose intolerance and IL-17/IFN-γ imbalance

Sun

Wang

et al. 2023

Cell. Mol. Life Sci.

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Adipose tissue CD11c+ myeloid cell is an independent risk factor associated with obesity and metabolic disorders. However, the underlying molecular basis remains elusive. Here, we demonstrated that liver kinase B1 (Lkb1), a key bioenergetic sensor, is involved in CD11c+ cell-mediated immune responses in diet-induced obesity. Loss of Lkb1 in CD11c+ cells results in obesity resistance but lower glucose tolerance, which accompanies tissue-specific immune abnormalities. The accumulation and CD80’s expression of Lkb1 deficient adipose-tissue specific dendritic cells but not macrophages is restrained. Additionally, the balance of IL-17A and IFN-γ remarkably tips towards the latter in fat T cells and CD11c− macrophages. Mechanistically, IFN-γ promotes apoptosis of preadipocytes and inhibits their adipogenesis while IL-17A promotes the adipogenesis in vitro, which might account in part for the fat gain resistant phenotype. In summary, these findings reveal that Lkb1 is essential for fat CD11c+ dendritic cells responding to HFD exposure and provides new insights into the IL-17A/IFN-γ balance in HFD-induced obesity.

show abstract

Section: Discussionsupporting

confidence: 92%

Loss of Lkb1 in CD11c+ myeloid cells protects mice from diet-induced obesity while enhancing glucose intolerance and IL-17/IFN-γ imbalance

Sun

Wang

et al. 2023

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…The dysregulation of IL-17A and IFN-γ in adipose tissue might be one of the critical contributors. Moreover, loss of Lkb1 in CD11c + cells remarkably increases splenic T cell responses under HFD exposure, which is consistent with other reported evidence on CD11c Cre Lkb1 f/f mice [28,29,37,38]. Additional experiments needs to explore whether the overactivated peripheral T cells affect the function of islet and further disturb the insulin secretion and glucose homeostasis.…”

Section: Discussionsupporting

confidence: 89%

“…CD11c + myeloid cells are involved in overnutrition associated immune-metabolic disorders [14,16,17,36], therefore, understanding of the underlying molecular basis becomes essential in developing intervention strategies for these threatens. Previous studies have revealed the critical role of the nutrient sensor Lkb1 in controlling the function of splenic and lymphoid CD11c + dendritic cells [28,29,37,38]. However, the specific role of Lkb1 in fat CD11c + cells, especially under the high-fat diet exposure, has not been addressed.…”

Section: Discussionmentioning

confidence: 99%

“…It is well recognized that selective deletion of Lkb1 in CD11c + dendritic cells enhances their capacity to prime effector T cell response and prevailingly expands Treg pools throughout the body [28,29,37,38]. Therefore, the decreased number of ATDCs possibly contribute to the decreased advantage of VAT-Treg from CD11c Cre Lkb1 f/f mice under HFD exposure.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Loss of Lkb1 disturbs adipose tissue dendritic cells and protects mice from obesity under high-fat feeding condition

Sun

Wang²,

et al. 2022

Preprint

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Adipose tissue CD11c + myeloid cell is an independent risk factor associated with obesity and metabolic disorders. However, the underlying molecular basis remains elusive. Here, we demonstrated that liver kinase B1 (Lkb1), a key bioenergetic sensor, is involved in CD11c + cell-mediated immune responses in diet-induced obesity. Loss of Lkb1 in CD11c + cells results in obesity resistance but lower glucose tolerance, which accompanies tissue-specific immune abnormalities. The accumulation and CD80’s expression of Lkb1 deficient adipose-tissue specific dendritic cells but not macrophages is restrained. Additionally, the balance of IL-17A and IFN-γ remarkably tips towards the latter in fat T cells and CD11c - macrophages. Mechanistically, IFN-γ promotes apoptosis of preadipocytes and inhibits their adipogenesis, which might account in part for the fat-resistant phenotype. In summary, these findings reveal that Lkb1 is essential for fat CD11c + dendritic cells responding to HFD exposure and provides new insights into the IL-17A/IFN-γ balance in HFD-induced obesity.

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“…Liver kinase b1 ( Lkb1 ) is a tumor suppressor that has been reported to be associated with many different types of cancer [ 11 , 12 , 13 ]. Moreover, Lkb1 also plays a crucial role in immune cells, including dendritic cells [ 14 , 15 , 16 , 17 ], macrophages, [ 18 ], and Treg [ 19 , 20 ]. We previously demonstrated that the Lkb1 signaling pathway is essential for maintaining Treg homeostasis by stabilizing Foxp3 expression [ 21 ].…”

mentioning

confidence: 99%

Lkb1 loss in regulatory T cells leads to dysregulation of hematopoietic stem cell expansion and differentiation in bone marrow

2023

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The tumor suppressor Lkb1 is known to regulate the expression of forkhead box P3 (Foxp3), thereby maintaining the levels of Foxp3+ regulatory T cells (Treg) that play a crucial role in self‐tolerance. However, the effect of Lkb1 in Treg on hematopoietic stem cells (HSCs) in the bone marrow (BM) remains obscure. Here, we demonstrated that conditional deletion of Lkb1 in Treg causes loss of Treg in the BM, which leads to failure of HSC homeostasis and the abnormal expansion. Moreover, the loss of BM Treg results in dysregulation of other developing progenitors/stem cell populations, leading to the defective differentiation of T cells and B cells. In addition, HSC from the BM with Treg loss exhibited poor engraftment efficiency, indicating that loss of Treg leads to irreversible impairment of HSC. Collectively, these results demonstrated the essential role of Lkb1 in Treg for maintaining HSC homeostasis and differentiation in mice. These findings provide insight into the mechanisms of HSC regulation and guidance for a strategy to improve the outcomes and reduce complications of HSC transplantation.

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LKB1 restrains dendritic cell function

Cited by 6 publications

References 12 publications

Loss of Lkb1 in CD11c+ myeloid cells protects mice from diet-induced obesity while enhancing glucose intolerance and IL-17/IFN-γ imbalance

Loss of Lkb1 in CD11c+ myeloid cells protects mice from diet-induced obesity while enhancing glucose intolerance and IL-17/IFN-γ imbalance

Loss of Lkb1 disturbs adipose tissue dendritic cells and protects mice from obesity under high-fat feeding condition

Lkb1 loss in regulatory T cells leads to dysregulation of hematopoietic stem cell expansion and differentiation in bone marrow

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