Frontiers in immunology · 2026
PD-1 deficiency reshapes the TCRβ repertoire and T-cell developmental programs associated with susceptibility to lupus-like autoimmunity.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hou Xianliang, Liu Zhenyu, Lu Guiya, Jiang Shaofeng, Qiu Jinjun, Li Chunhong, Meng Meng, Hu Zipeng, Lei Yinping, Lao Huilin, Chen Lemin, Wen Yue, Xie Siyan, Liang Yuqiang
Аннотация
INTRODUCTION: Programmed cell death protein-1 (PD-1) functions as a pivotal immune checkpoint, essential for maintaining peripheral immune tolerance, and serves as a significant therapeutic target in cancer immunotherapy. Nevertheless, the relationship between PD-1 deficiency and baseline alterations in T-cell receptor (TCR) repertoire organization, as well as the susceptibility to lupus-like autoimmunity, remains inadequately elucidated.
METHODS: In this study, we integrated immune repertoire sequencing with bulk RNA sequencing of peripheral blood mononuclear cells (PBMCs) to delineate the organization of the TCRβ repertoire and genotype-associated transcriptional changes in PD-1-deficient mice. To assess autoimmune susceptibility following an environmental immune challenge, we utilized a Campylobacter jejuni (CJ-S131)-induced lupus-like autoimmune model.
RESULTS: Our findings revealed that PD-1-deficient mice exhibited alterations in TCRβ repertoire diversity, complementarity-determining region 3 (CDR3) length distributions, TRBV/TRBJ segment usage, V-D-J recombination patterns, and clonotype abundance. Through transcriptomic analysis, we identified significant alterations in the expression of genes linked to lymphocyte development and the maintenance of the T-cell receptor (TCR) repertoire. Concurrently, our predicted regulatory-network analysis highlighted FOXC1, E2F1, GATA2, and MEF2A as potential upstream transcription factors implicated in subsets of these transcriptional changes. PD-1 deficiency was correlated with modified proportions of T cells, natural killer (NK) cells, B cells, and the CD4+CD25+CD127low/- putative regulatory T-cell population. Additionally, PD-1-deficient splenocytes demonstrated heightened proliferative responses upon polyclonal stimulation. In the context of CJ-S131-induced autoimmune challenge, PD-1-deficient mice exhibited elevated levels of lupus-associated autoantibodies and more severe lupus-like renal pathology.
DISCUSSION: Collectively, our findings suggest that PD-1 deficiency is linked to disrupted TCRβ repertoire organization, extensive immune dysregulation, and an increased vulnerability to infection-induced lupus-like autoimmunity.
METHODS: In this study, we integrated immune repertoire sequencing with bulk RNA sequencing of peripheral blood mononuclear cells (PBMCs) to delineate the organization of the TCRβ repertoire and genotype-associated transcriptional changes in PD-1-deficient mice. To assess autoimmune susceptibility following an environmental immune challenge, we utilized a Campylobacter jejuni (CJ-S131)-induced lupus-like autoimmune model.
RESULTS: Our findings revealed that PD-1-deficient mice exhibited alterations in TCRβ repertoire diversity, complementarity-determining region 3 (CDR3) length distributions, TRBV/TRBJ segment usage, V-D-J recombination patterns, and clonotype abundance. Through transcriptomic analysis, we identified significant alterations in the expression of genes linked to lymphocyte development and the maintenance of the T-cell receptor (TCR) repertoire. Concurrently, our predicted regulatory-network analysis highlighted FOXC1, E2F1, GATA2, and MEF2A as potential upstream transcription factors implicated in subsets of these transcriptional changes. PD-1 deficiency was correlated with modified proportions of T cells, natural killer (NK) cells, B cells, and the CD4+CD25+CD127low/- putative regulatory T-cell population. Additionally, PD-1-deficient splenocytes demonstrated heightened proliferative responses upon polyclonal stimulation. In the context of CJ-S131-induced autoimmune challenge, PD-1-deficient mice exhibited elevated levels of lupus-associated autoantibodies and more severe lupus-like renal pathology.
DISCUSSION: Collectively, our findings suggest that PD-1 deficiency is linked to disrupted TCRβ repertoire organization, extensive immune dysregulation, and an increased vulnerability to infection-induced lupus-like autoimmunity.