Immune phenotype of the CD4+ T cells in the aged lymphoid organs and lacrimal glands

Trujillo-Vargas, Claudia M.; Hernandez, Humberto; Souza, Rodrigo G. de; Yu, Zhiyuan; Galletti, Jeremías Gastón; Dietrich, Jana; Paulsen, Friedrich; Paiva, Cintia S. de

doi:10.1007/s11357-022-00529-z

Cited by 12 publications

(16 citation statements)

References 101 publications

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“…The main characteristic of aged lacrimal glands is chronic inflammatory changes characterized by lymphocytic infiltration. 20 , 52 , 53 To understand these features, we first compared the changes in the number of CD3 + lymphocytes ( Figs. 3 C, 3 D), CD19 + B cells ( Figs.…”

Section: Resultsmentioning

confidence: 99%

Mechanisms of Extraorbital Lacrimal Gland Aging in Mice: An Integrative Analysis of the Temporal Transcriptome

Liu,

Si,

Huang

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose This study used high-throughput RNA sequencing (RNA-Seq) and bioinformatics analysis to investigate the altered transcriptome profile of aging lacrimal glands in mice that occurs over the course of a 24-hour cycle. Methods Male C57BL/6J mice aged 12 weeks (young) and 20 months (aging) were housed in a pathogen-free setting with a 12-hour light/12-hour dark cycle. Throughout a 24-hour cycle, mouse extraorbital lacrimal glands (ELGs) were collected at eight time points at three-hour intervals. To prepare for the high-throughput RNA-Seq, whole mRNA was extracted. Differentially expressed genes (DEGs) in the young and aging groups were subjected to bioinformatic analysis based on diurnal patterns. Furthermore, the cell populations in which significant DEGs express and signaling pathways occur were validated at the single-cell RNA sequencing (scRNA-seq) level. Results The total transcriptome composition was significantly altered in aging ELGs compared with that in young mouse ELGs at eight time points during the 24-hour cycle, with 864 upregulated and 228 downregulated DEGs, which were primarily enriched in inflammatory pathways. Further comparative analysis of the point-to-point transcriptome revealed that aging ELGs underwent alterations in the temporal transcriptome profile in several pathways, including the inflammation-related, metabolism-related, mitochondrial bioenergetic function–associated, synaptome neural activity–associated, cell processes–associated, DNA processing–associated and fibrosis–associated pathways. Most of these pathways occurred separately in distinct cell populations. Conclusions Transcriptome profiles of aging lacrimal glands undergo considerable diurnal time-dependent changes; this finding offers a comprehensive source of information to better understand the pathophysiology of lacrimal gland aging and its underlying mechanisms.

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Section: Resultsmentioning

confidence: 99%

Mechanisms of Extraorbital Lacrimal Gland Aging in Mice: An Integrative Analysis of the Temporal Transcriptome

Liu,

Si,

Huang

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

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“…In the search of mechanisms that can counteract the effects of the overwhelming immune infiltration, we started characterizing one of the main players of immune tolerance, the thymic-derived T regulatory cells (Tregs). Tregs possess the ability to hamper the activation of conventional T cells through a variety of mechanisms [ 3 ]. But let’s stay within the frame of "Men in Black", where human-like beings turn into aliens on multiple occasions: similar scenery happens with the tolerogenic Tregs in the aged gland.…”

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confidence: 99%

“…But let’s stay within the frame of "Men in Black", where human-like beings turn into aliens on multiple occasions: similar scenery happens with the tolerogenic Tregs in the aged gland. They express all the markers that support their suppressive function but paradoxically, seem highly differentiated and infiltrative, actively produce inflammatory cytokines, possess defective suppressive capabilities and more importantly, recapitulate lacrimal gland pathology when adoptively transferred to immunodeficient recipients [ 3 , 4 ]. Moreover, in the aged lacrimal gland, Tregs are surrounded by CD4+ T cells that are highly differentiated towards the effector Th1 and Th17 phenotype and have features compatible with exhaustion and immunopathology [ 3 ].…”

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confidence: 99%

“…They express all the markers that support their suppressive function but paradoxically, seem highly differentiated and infiltrative, actively produce inflammatory cytokines, possess defective suppressive capabilities and more importantly, recapitulate lacrimal gland pathology when adoptively transferred to immunodeficient recipients [ 3 , 4 ]. Moreover, in the aged lacrimal gland, Tregs are surrounded by CD4+ T cells that are highly differentiated towards the effector Th1 and Th17 phenotype and have features compatible with exhaustion and immunopathology [ 3 ]. These characteristics seem to make it more difficult for Tregs to exert their immunosuppressive function.…”

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confidence: 99%

“…We observed that Tregs in the aged gland expressed high levels of Il1r2 , CD81 , and Tbx21 , among others. Tbx21 is also highly expressed by conventional T cells [ 3 ] and increased expression of CD79a/b is observed in activated B cells [ 1 ]. A systematic review of biological therapies for Sjögren’s syndrome, an autoimmune disease that represent “the tip of the iceberg”, i.e., the most severe presentation of the sicca syndrome in exocrine glands, described 25 promising ongoing clinical trials that target lymphocyte signaling and function and other inflammatory pathways [ 8 ].…”

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confidence: 99%

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