Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche

Li, Zhi; Hu, Xianting; Liang, Yuqiong; Yu, Jenwei; Li, Hua-Bin; Shokhirev, Maxim N.; Zheng, Ye

doi:10.1038/s41590-022-01244-9

Cited by 47 publications

(26 citation statements)

References 72 publications

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“…Cloning of sgRNAs into the pSIRG-NGFR vector, and retrovirus production in HEK293T cells were performed as previously described 43 . Details of sgRNA sequence are listed in Supplementary Table 2.…”

Section: Methodsmentioning

confidence: 99%

Foxp3 Orchestrates Reorganization of Chromatin Architecture to Establish Regulatory T Cell Identity

Lee

Liang

et al. 2023

Preprint

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Chromatin conformation reorganization is emerging as an important layer of regulation for gene expression and lineage specification. Yet, how lineage-specific transcription factors contribute to the establishment of cell type-specific 3D chromatin architecture in the immune cells remains unclear, especially for the late stages of T cell subset differentiation and maturation. Regulatory T cells (Treg) are mainly generated in the thymus as a subpopulation of T cells specializing in suppressing excessive immune responses. Here, by comprehensively mapping 3D chromatin organization during Treg cell differentiation, we show that Treg-specific chromatin structures were progressively established during its lineage specification, and highly associated with Treg signature gene expression. Additionally, the binding sites of Foxp3, a Treg lineage specifying transcription factor, were highly enriched at Treg-specific chromatin loop anchors. Further comparison of the chromatin interactions between wide-type Tregs versus Treg cells from Foxp3 knock-in/knockout or newly-generated Foxp3 domain-swap mutant mouse revealed that Foxp3 was essential for the establishment of Treg-specific 3D chromatin architecture, although it was not dependent on the formation of the Foxp3 domain-swapped dimer. These results highlighted an underappreciated role of Foxp3 in modulating Treg-specific 3D chromatin structure formation.

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Section: Methodsmentioning

confidence: 99%

Foxp3 Orchestrates Reorganization of Chromatin Architecture to Establish Regulatory T Cell Identity

Lee

Liang

et al. 2023

Preprint

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“…In line with these findings, Camacho et al recently demonstrated that BM Tregs regulate hematopoiesis indirectly through modulation of stromal cell function via secretion of IL-10 (29) (Figure 1 and Tables 1, 2). The role of Tregs in the regulation of stem cells, however, is not a unique feature for the BM and can be further extrapolated to multiple non-lymphoid tissues such as for example the skin, muscle, adipose tissue and brain (46)(47)(48)(49). Consequently, accumulating scientific evidence supports the concept that Tregs control stem cells, their proliferation and self-renewal.…”

Section: Regulatory T Cells In Hematopoiesismentioning

confidence: 99%

Regulation of hematopoietic and leukemia stem cells by regulatory T cells

Riether

2022

Front. Immunol.

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Adult bone marrow (BM) hematopoietic stem cells (HSCs) are maintained in a quiescent state and sustain the continuous production of all types of blood cells. HSCs reside in a specialized microenvironment the so-called HSC niche, which equally promotes HSC self-renewal and differentiation to ensure the integrity of the HSC pool throughout life and to replenish hematopoietic cells after acute injury, infection or anemia. The processes of HSC self-renewal and differentiation are tightly controlled and are in great part regulated through cellular interactions with classical (e.g. mesenchymal stromal cells) and non-classical niche cells (e.g. immune cells). In myeloid leukemia, some of these regulatory mechanisms that evolved to maintain HSCs, to protect them from exhaustion and immune destruction and to minimize the risk of malignant transformation are hijacked/disrupted by leukemia stem cells (LSCs), the malignant counterpart of HSCs, to promote disease progression as well as resistance to therapy and immune control. CD4+ regulatory T cells (Tregs) are substantially enriched in the BM compared to other secondary lymphoid organs and are crucially involved in the establishment of an immune privileged niche to maintain HSC quiescence and to protect HSC integrity. In leukemia, Tregs frequencies in the BM even increase. Studies in mice and humans identified the accumulation of Tregs as a major immune-regulatory mechanism. As cure of leukemia implies the elimination of LSCs, the understanding of these immune-regulatory processes may be of particular importance for the development of future treatments of leukemia as targeting major immune escape mechanisms which revolutionized the treatment of solid tumors such as the blockade of the inhibitory checkpoint receptor programmed cell death protein 1 (PD-1) seems less efficacious in the treatment of leukemia. This review will summarize recent findings on the mechanisms by which Tregs regulate stem cells and adaptive immune cells in the BM during homeostasis and in leukemia.

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“…Additionally, structures such as hair follicles and nerve endings are major players in regulating immune responses in the skin. Hair follicles represent unique structures in the skin, as many studies in mice have shown that they are the primary site for T reg maintenance, which are in turn essential for establishing the stem cell niche at the hair follicle ( 67 – 69 ). In human skin, the hair follicle is also the major site of T reg localization ( 70 ).…”

Section: Skinmentioning

confidence: 99%

(Not) Home alone: Antigen presenting cell – T Cell communication in barrier tissues

2022

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Priming of T cells by antigen presenting cells (APCs) is essential for T cell fate decisions, enabling T cells to migrate to specific tissues to exert their effector functions. Previously, these interactions were mainly explored using blood-derived cells or animal models. With great advances in single cell RNA-sequencing techniques enabling analysis of tissue-derived cells, it has become clear that subsets of APCs are responsible for priming and modulating heterogeneous T cell effector responses in different tissues. This composition of APCs and T cells in tissues is essential for maintaining homeostasis and is known to be skewed in infection and inflammation, leading to pathological T cell responses. This review highlights the commonalities and differences of T cell priming and subsequent effector function in multiple barrier tissues such as the skin, intestine and female reproductive tract. Further, we provide an overview of how this process is altered during tissue-specific infections which are known to cause chronic inflammation and how this knowledge could be harnessed to modify T cell responses in barrier tissue.

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Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche

Cited by 47 publications

References 72 publications

Foxp3 Orchestrates Reorganization of Chromatin Architecture to Establish Regulatory T Cell Identity

Foxp3 Orchestrates Reorganization of Chromatin Architecture to Establish Regulatory T Cell Identity

Regulation of hematopoietic and leukemia stem cells by regulatory T cells

(Not) Home alone: Antigen presenting cell – T Cell communication in barrier tissues

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