Biology subjects

Bjorkstrom, N. K.

Publications and source records attributed to Bjorkstrom, N. K..

5 recordsLinked to original sources

bioRxiv2024

Distinct tissue-dependent composition and gene expression of human fetal innate lymphoid cells

The human fetal immune system starts to develop in the first trimester and likely plays a crucial role in fetal development and maternal-fetal tolerance. Innate lymphoid cells (ILCs) are the earliest lymphoid cells to arise in the human fetus. ILCs consists of natural killer (NK) cells, ILC1s, ILC2s, and ILC3s that all share a common lymphoid origin. Here, we studied fetal ILC subsets, mainly NK cells and ILC3s and their potential progenitors, across human fetal tissues from the first and second trimesters. Our results show that fetal ILC subsets have distinct distribution, developmental kinetics, and gene expression profiles across human fetal tissues. Furthermore, we identify a putative CD34+ROR{gamma}t+Eomes+/- ILC progenitor population exclusively present in fetal intestine, indicating that tissue-restricted development of ILCs could contribute to the variation in ILC composition and gene expression between tissues.

immunology↗

bioRxiv2024

Reconstitution of the uterine immune milieu after transplantation

Maintenance of tissue-specific immunity is important for immunological fitness, but its establishment have been difficult to assess in humans. Here, we investigated reconstitution of the human uterine immune system by studying women undergoing uterus solid organ transplantation (UTX) or hematopoietic stem cell transplantation (HSCT). Through single-cell identification based on SNPs and disparate HLA expression using single-cell RNA sequencing or high-parameter flow cytometry, donor vs recipient cell origin was determined, and features of these cells were studied. A full uterine immune cell reconstitution occurred after both UTX and HSCT, both at transcriptomic and phenotypic level. This occurred despite tacrolimus-induced calcineurin-mediated NFAT pathway inhibition, which affected de novo induction of tissue-residency features in vitro. Intriguingly, after HSCT, immune cells of male origin could reconstitute the uterine immune milieu. Collectively, our results proved insights into tissue immune system persistence and reconstitution capabilities in an organ undergoing continuous regeneration.

immunology↗

bioRxiv2022

Protection from liver cancer in a mouse model of Alagille syndrome follows dysregulated differentiation of thymocytes and hepatocytes

Fibrosis is a physiological tissue repair mechanism, but excessive fibrosis can disrupt organ function. Alagille syndrome (ALGS), which is caused by mutations in the Notch ligand JAGGED1, results in bile duct paucity, neonatal cholestasis, and a characteristic fibrotic response. Here, we show that Jag1Ndr/Ndr mice, a model for ALGS, recapitulates ALGS-like pericellular fibrosis. Single-cell RNA-seq and multi-color flow cytometry characterization of the liver and spleen revealed immature hepatocytes and paradoxically low intrahepatic T cell infiltration in cholestatic Jag1Ndr/Ndr mice, despite an enrichment in extrahepatic (thymic and splenic) regulatory T cells (Tregs). Jag1Ndr/Ndr lymphocyte immune and fibrotic capacity was tested with adoptive immune cell transplantation into Rag1-/- mice, challenged with dextran sulfate sodium (DSS) or bile duct ligation (BDL). Transplanted Jag1Ndr/Ndr lymphocytes were less inflammatory with fewer activated T cells than Jag1+/+ lymphocytes, in response to DSS. Cholestasis induced by BDL in Rag1-/- mice with Jag1Ndr/Ndr lymphocytes resulted in periportal Treg accumulation and three-fold less periportal fibrosis than in Rag1-/- mice with Jag1+/+ lymphocytes. Finally, we show that the Jag1Ndr/Ndr hepatocyte expression profile and Treg overrepresentation are corroborated by transcriptomic data from children with ALGS. In sum, these data lead to a model in which Jag1-driven developmental hepatic and immune defects interact to determine the fibrotic process in ALGS.

developmental biology↗

bioRxiv2020

The identity of human tissue-emigrant CD8+ T cells

Lymphocyte migration is essential for human adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies to date have been restricted to immunological analyses of blood and various tissues. To address this issue, we used an integrated approach to characterize tissue-emigrant immune cells in thoracic duct lymph (TDL). In humans and non-human primates, lymphocytes were by far the most abundant immune lineage population in efferent lymph, and a vast majority of these lymphocytes were T cells. Cytolytic CD8+ T cell subsets were clonotypically discrete and selectively confined to the intravascular circulation, persisting for months after inhibition of S1P-dependent tissue egress by FTY-720. In contrast, non-cytolytic CD8+ T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Collectively, these data provide an atlas of the migratory immune system and define the nature of tissue-emigrant CD8+ T cells that recirculate via TDL.

immunology↗

bioRxiv2020

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

ABSTRACTSARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology↗