Biology subjects

Ritter, J.

Publications and source records attributed to Ritter, J..

4 recordsLinked to original sources

bioRxiv2026

SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells

The chromatin organizer SATB1 is indispensable for thymic regulatory T cell (Treg cell) development and T helper cell induction. Several gene loci have been described to be SATB1-controlled, including the transcription factor GATA3 and the cytokine loci IL-4 and IL-17. However, the global effects of SATB1 on fully differentiated human CD4 conventional T cells (Tconv cells) and Treg cells, and thus SATB1s potential as a target for T cell engineering, are poorly understood. We describe SATB1-regulated gene signatures as largely subset-specific, with broader effects on Treg cells. Despite of the distinct gene-regulatory patterns, we observe overarching dysregulated cytokine and JAK-STAT signaling after SATB1 ablation. Functionally, SATB1 KO reduces human Treg cell suppressive capacities but boosts tumor clearance via CD4 CAR T cells in a preclinical, humanized mouse model. Together, Treg destabilization and simultaneous increased activation of CD4 CAR T cells by SATB1 modulation may be an interesting strategy to boost the efficiency of CAR T cell therapies.

immunology↗

bioRxiv2025

Miniaturized Device for Assessing Calcification Propensity of Biohybrid Implants Under Continuous Flow

Biohybrid implants are a promising development for cardiovascular disease treatment but suffer from problems like thrombogenesis and calcification. However, testing and validating biohybrid implants can be difficult and expensive due to material handling, fabrication methods and specialty medium components. The devices used to test potential samples can be large and expensive, requiring significant amounts of cell culture medium to operate. Additional, conventional static cell culture conditions do not accurately represent the vascular environment as shear and mechanical forces play key roles in the development of calcification. To address these challenges, a miniaturized, dual-channel flow chamber was designed and validated that allowed for real-time visualization of biohybrid calcification in a physiological environment. Computational Fluid Dynamics simulations were performed to determine the flow characteristics that generated physiological shear stress homogeneously across the sample surface. Micro particle tracking velocimetry measurements validated the simulated shear stresses near the sample surface. Two implant materials used for biohybrid construction, bovine pericardium and polycarbonate urethane, were inserted in the device and exposed to a flowing calcification medium for 14 days. Fluorescent fetuin-A was introduced into the calcification medium for real-time calcification monitoring. The two materials were compared with matched samples calcified in a large fatigue tester for 14 days. Our results showed similar material calcification for bovine pericardium and no calcification for polycarbonate urethane in the large fatigue tester and in our newly developed device. Biohybrid textile-reinforced fibrin-based scaffold populated with vascular smooth muscle cells started to calcify over 7 days in calcification medium. We conclude that this platform will provide novel insights into the origin and progression of pathological calcification and its potentially harmful health effects, which can occur as a result of tissue or metabolic abnormalities, disease, or implantation of certain biomaterials, by providing the ability to monitor the progression of calcification in biohybrid implants in real time, while also minimizing the cost and size of samples and reagents required for testing.

bioengineering↗

bioRxiv2023

Nanos2+ cells give rise to germline and somatic lineages in the sea anemone Nematostella vectensis

In all animals, stem cell populations of varying potency facilitate regeneration and tissue homeostasis. Notably, germline stem cells in both vertebrates and invertebrates express highly conserved RNA-binding proteins, such as nanos, vasa and piwi. Interestingly, in animals, which are capable of whole-body regeneration, such as poriferans, hydrozoans and planarians, these genes are also expressed in somatic multi- and pluripotent stem cells, which led to the proposal that they had an ancestral role in all stem cells. While multi- and pluripotent interstitial stem cells have been identified in hydrozoans, they have not unambiguously been demonstrated in other cnidarian classes. Therefore, it is currently unclear if these stem cell systems share a common evolutionary origin or have been adapted individually in different lineages as homoplasy. We therefore aimed to characterize stem cells expressing conserved stem cell marker genes in the sea anemone Nematostella vectensis, to gain insight of shared traits governing the regulation of this enigmatic cell type. Through single cell transcriptomics, we identify cell populations expressing the germline associated markers piwi1 and nanos2 in the soma and germline. Transgenic reporter genes reveal a lineage giving rise to somatic cells, consistent with a role as a multipotent stem cell population. Cell proliferation studies show that a fraction of nanos2+ reporter cells are cycling and CRISPR/Cas9 mediated gene knockout show that nanos2+ progenitor cells are indispensable for male and female germline maintenance in Nematostella. This suggests nanos and piwi genes have a conserved role in somatic and germline stem cells in cnidarians.

developmental biology↗

bioRxiv2021

Reconstitution of T cell immunity against EBV in the immunocompromised host by adoptive transfer of peptide-stimulated T cells after allogeneic stem cell transplantation

Reconstitution of T cell repertoire after allogeneic stem cell transplantation is a long and often incomplete process. As a result, reactivation of Epstein-Barr virus (EBV) is a frequent complication that may be treated by adoptive transfer of donor-derived EBV-specific T cells. We generated donor-derived EBV-specific T cells by peptide stimulation and adoptively transferred them to a patient with angioimmunoblastic T-cell lymphoma (AITL), who had developed persisting high titers of EBV concomitant to relapse after transplantation. T cell receptor beta (TCR{beta}) deep sequencing showed that the T cell repertoire of the patient early after transplantation (day 60) was strongly reduced and only very low numbers of EBV-specific T cells were detectable. Manufacturing and in vitro expansion of donor-derived EBV-specific T cells resulted in enrichment of EBV epitope-specific, HLA-restricted T cells. Monitoring after adoptive transfer revealed that the dominant TCR sequences from peptide-stimulated T cells persisted long-term and established an EBV-specific TCR clonotype repertoire in the host, with many of the EBV-specific TCRs present in the donor. This reconstituted repertoire was associated with immunological control of EBV and with lack of further AITL relapse. Author summaryA characteristic feature of all herpesviruses is their persistence in the hosts body after primary infection. Hence, the hosts immune system is confronted with the problem to control these viruses life-long. Well-known representative of the herpesvirus group are the classic Herpes-Simplex Virus (HSV-1) and Varicella Zoster Virus (VZV, causing chicken pox); a less known representative is Epstein Barr Virus (EBV, causing mononucleosis). When the immune system is severely compromised, for example after stem cell transplantation from a foreign (allogeneic) donor, these viruses can reappear, as they are already in the hosts body. Especially EBV cause life-threatening complications after stem cell transplantation and only reinforcement of the hosts immune system can reestablish viral control. Here we show that ex vivo manufactured EBV-specific T cells can reestablish long-term control of EBV and that these cells persist in the hosts body over months. These results give us a better understanding of viral immune reconstitution post-transplant and of clinically-relevant T cell populations against EBV.

immunology↗