Thymus involution sets the clock of the aging T-cell landscape: Implications for declined immunity and tissue repair

Elyahu, Yehezqel; Monsonego, Alon

doi:10.1016/j.arr.2020.101231

Cited by 46 publications

(25 citation statements)

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“…LNs mainly consist of T cells and B cells, where they are activated by encountering antigen (Gasteiger et al, 2016 ). T cells and B cells are the main components of adaptive immunity; therefore, they have been the focus of studies on aging and immunity (Goronzy and Weyand, 2019 ; Elyahu and Monsonego, 2021 ). Thus, we next examined aging-induced alterations in T cells and B cells.…”

Section: Resultsmentioning

confidence: 99%

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Zhu

Wang

et al. 2021

Protein Cell

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Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs’ effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.

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Section: Resultsmentioning

confidence: 99%

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Zhu

Wang

et al. 2021

Protein Cell

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“…Ageing is associated with a gradual expansion of circulating myeloid cell populations relative to lymphoid cell populations 15 (Table 1 ). In part, this shift is due to a decline in thymic activity required for the generation of nascent T cells 16 . At the same time, there is a differential effect of age on early myelopoiesis and lymphopoiesis in the bone marrow 17 .…”

Section: Effects Of Ageing On Myeloid Cellsmentioning

confidence: 99%

Immune ageing at single-cell resolution

2021

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“…Overall, we reported a primary scRNA-seq analysis of the human corneal innate and adaptive immune cell types, including antiviral effector CD8 + T cells, naive T cells, and innate immune cells such as IDO1 + mregDCs, macrophages, monocytes, and basophils, providing a detailed map of corneal immune cell function. It should be noted that, because aging could lead to changes in the immune system, such as the distribution and number of immune cells ( 27 , 28 ), despite using similar numbers of cells from each donor, the wide donor-to-donor age variation could affect the results to a certain extent. We identified subtype-specific transcriptional factors and surface markers for the different immune cell types.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characteristics and Distribution of Adult Human Corneal Immune Cell Types

Jeong

Song

2022

Front. Immunol.

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BackgroundThe limbus is located at a 2-mm-wide area between the bulbar conjunctiva and the cornea and has been suggested to be the niche of corneal epithelial stem cells and immune cells. Like the skin and intestines, the cornea is also an important mucosal surface, and immune cells on the cornea play critical roles in immune surveillance to ensure barrier surface homeostasis and protection from various environmental damage and infections. Single-cell RNA sequencing (scRNA-seq) analysis of protein tyrosine phosphatase receptor type C positive (PTPRC+) hematopoietic cells from the corneal limbus could provide a single cell atlas of all the immune cell subsets.MethodsWe performed single-cell RNA sequencing to generate transcriptomic profile for 804 sort-purified hematopoietic cells from the corneal limbus of three healthy donors.ResultsOur analysis identified a primary transcriptomic pattern for multiple immune cell subtypes, including naive T cells, antiviral effector CD8+ T cells, and innate immune cells such as IDO1+ mature regulatory dendritic cells (mregDCs), macrophages, monocytes, and basophils in the human corneal limbus.ConclusionOverall, single-cell transcriptomic analysis of limbal immune cells suggested the possible contribution of these cells on the adaptive and innate immune response of the human cornea.

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Thymus involution sets the clock of the aging T-cell landscape: Implications for declined immunity and tissue repair

Cited by 46 publications

References 253 publications

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Immune ageing at single-cell resolution

Molecular Characteristics and Distribution of Adult Human Corneal Immune Cell Types

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