Diffusion-limited cytokine signaling in T cell populations.

Effective immune-cell responses depend on collective decision-making mediated by diffusible intercellular signaling proteins called cytokines. Here, we designed a three-dimensional spatiotemporal modeling framework and a precise finite-element simulation setup to systematically investigate the origin and consequences of spatially inhomogeneous cytokine distributions in lymph nodes. We found that such inhomogeneities are critical for effective paracrine signaling, and they do not arise by diffusion and uptake alone, but rather depend on properties of the cell population such as an all-or-none behavior of cytokine secreting cells.

Reverse Genetics Applied to Immunobiology of Tumor Necrosis Factor, a Multifunctional Cytokine.

Tumor necrosis factor (TNF) is one of many cytokines - protein molecules responsible for communication between the cells of immune system. TNF was discovered and given its grand name because of its striking antitumor effects in experimental systems, but its main physiological functions in the context of whole organism turned out to be completely unrelated to protection against tumors. This short review discusses "man-made" mouse models generated by early genome-editing technologies, which enabled us to establish true functions of TNF in health and certain diseases as well as to unravel potential strategies for improving therapy of TNF-dependent diseases.

Plasticity and lineage commitment of individual T1 cells are determined by stable T-bet expression quantities.

T helper 1 (T1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated T1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection.

Factors associated with disease flare following SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: results from the physician-reported EULAR Coronavirus Vaccine (COVAX) Registry.

Objectives: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs).

Methods: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors.

Psychosocial Burden During the COVID-19 Pandemic in Adolescents With Type 1 Diabetes in Germany and Its Association With Metabolic Control.

Purpose: To investigate the psychosocial burden during the COVID-19 pandemic in adolescents with type 1 diabetes and its association with metabolic control.

Methods: Prospective multicenter observational cohort study based on data from the German Diabetes Prospective Follow-up Registry. Adolescents aged 12-20 years with type 1 diabetes were asked during routine follow-up visits to complete a questionnaire on psychosocial distress and daily use of electronic media during the COVID-19 pandemic from June 2021 to November 2022.

A type 1 immunity-restricted promoter of the IL-33 receptor gene directs antiviral T-cell responses.

The pleiotropic alarmin interleukin-33 (IL-33) drives type 1, type 2 and regulatory T-cell responses via its receptor ST2. Subset-specific differences in ST2 expression intensity and dynamics suggest that transcriptional regulation is key in orchestrating the context-dependent activity of IL-33-ST2 signaling in T-cell immunity. Here, we identify a previously unrecognized alternative promoter in mice and humans that is located far upstream of the curated ST2-coding gene and drives ST2 expression in type 1 immunity.

- friend or foe in colorectal cancer?

is a gram-negative anaerobic bacterium, which represents a part of the commensal human microbiota. Decline in the abundance of among other microbial species in the gut correlates with severe systemic diseases such as diabetes, obesity, intestinal inflammation and colorectal cancer. Due to its mucin-reducing and immunomodulatory properties, the use of probiotics containing sp.

Inactivated whole virion vaccine protects K18-hACE2 Tg mice against the Omicron SARS-CoV-2 variant via cross-reactive T cells and nonneutralizing antibody responses.

COVID-19 is a systemic inflammatory disease initiated by SARS-CoV-2 virus infection. Multiple vaccines against the Wuhan variant of SARS-CoV-2 have been developed including a whole virion beta-propiolactone-inactivated vaccine based on the B.1.

Regulatory T cells inhibit autoantigen-specific CD4 T cell responses in lupus-prone NZB/W F1 mice.

Introduction: Progressive loss of regulatory T cell (Treg)-mediated control over autoreactive effector T cells contributes to the development of systemic lupus erythematosus (SLE). Accordingly, we hypothesized that Treg may also have the capacity to suppress the activation of autoreactive CD4 T cells that are considered to drive autoimmunity.

Methods: To investigate whether Treg are involved in the control of autoreactive CD4 T cells, we depleted CD25 Treg cells either or , or combined both approaches before antigen-specific stimulation with the SLE-associated autoantigen SmD1(83-119) in the NZB/W F1 mouse model either after immunization against SmD1(83-119) or during spontaneous disease development.

Immune signatures of checkpoint inhibitor-induced autoimmunity-A focus on neurotoxicity.

Background: Neurologic immune-related adverse events (irAE-n) are rare but severe toxicities of immune checkpoint inhibitor (ICI) treatment. To overcome diagnostic and therapeutic challenges, a better mechanistic understanding of irAE-n is paramount.

Methods: In this observational cohort study, we collected serum and peripheral blood samples from 34 consecutive cancer patients with irAE-n (during acute illness) and 49 cancer control patients without irAE-n (pre- and on-ICI treatment, n = 44 without high-grade irAEs, n = 5 with high-grade nonneurologic irAEs).

Distribution modeling quantifies collective T cell decision circuits in chronic inflammation.

Immune responses are tightly regulated by a diverse set of interacting immune cell populations. Alongside decision-making processes such as differentiation into specific effector cell types, immune cells initiate proliferation at the beginning of an inflammation, forming two layers of complexity. Here, we developed a general mathematical framework for the data-driven analysis of collective immune cell dynamics.

Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort.

Background: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), concomitant depression might have a negative impact on the course of disease and treatment outcomes. The aims of this analysis are to determine the prevalence of depressive symptoms in axSpA and PsA patients in a real-world cohort study and to identify sociodemographic and clinical associated factors for moderate or severe depressive symptoms in both diseases.

Methods: Patients from the RABBIT-SpA cohort with an axSpA or PsA diagnosis and a valid WHO-5 Well-Being Index score at baseline were included.

Shared and Distinct Gut Microbiota in Spondyloarthritis, Acute Anterior Uveitis, and Crohn's Disease.

Objective: Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with nonmusculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn's disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology.

Methods: We performed 16S ribosomal RNA sequencing on stool samples of 277 patients (72 CD, 103 AAU, and 102 SpA) included in the German Spondyloarthritis Inception Cohort and 62 back pain controls without any inflammatory disorder.

Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients.

Tacrolimus is the backbone of immunosuppressive agents to prevent transplant rejection. Paradoxically, tacrolimus is nephrotoxic, causing irreversible tubulointerstitial damage. Therefore, infusion of mesenchymal stromal cells (MSC) 6 and 7 weeks post-transplantation was assessed to facilitate withdrawal of tacrolimus in the randomized phase II TRITON trial.

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1 CD8 T cells in chronic viral infection.

T cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these stem-like CD8 T cells (CD8SL) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection, we identified the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8SL as well as for virus control.

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

Objectives: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

Methods: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death.

IL-17A-producing CD8 T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8 T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC.

Embryonic ILC-poiesis across tissues.

The family of innate lymphoid cells (ILCs), consisting of Group 1 ILCs (natural killer cells and ILC1), ILC2, and ILC3, are critical effectors of innate immunity, inflammation, and homeostasis post-natally, but also exert essential functions before birth. Recent studies during critical developmental periods in the embryo have hinted at complex waves of tissue colonization, and highlighted the breadth of multipotent and committed ILC progenitors from both classic fetal hematopoietic organs such as the liver, as well as tissue sites such as the lung, thymus, and intestine. Assessment of the mechanisms driving cell fate and function of the ILC family in the embryo will be vital to the understanding ILC biology throughout fetal life and beyond.

Optimization of chondrocyte isolation from human articular cartilage to preserve the chondrocyte transcriptome.

The isolation of chondrocytes from human articular cartilage for single-cell RNA sequencing requires extensive and prolonged tissue digestion at 37 C. Modulations of the transcriptional activity likely take place during this period such that the transcriptomes of isolated human chondrocytes no longer match their original status . Here, we optimized the human chondrocyte isolation procedure to maximally preserve the transcriptome.

To kill or not to kill - The role of the tumor microenvironment in shaping group 1 ILC functions.

Group 1 innate lymphoid cells (ILC) comprise two major IFN-γ producing populations, namely Natural Killer (NK) cells, and ILC1s. Recent studies have revealed a complex and diverse composition of group 1 ILC subsets infiltrating different tumors. In this review, we will outline the commonalities and differences between group 1 ILC subsets in both mice and humans, discuss how the tissue and tumor microenvironment shapes their phenotype and functions, as well as describe their contrasting roles in the response to different cancers.

Induction of cross-reactive, mucosal anti-SARS-CoV-2 antibody responses in rheumatoid arthritis patients after 3rd dose of COVID-19 vaccination.

Systemic vaccination against SARS-CoV-2 elicited high titers of specific antibodies in the blood and in the oral cavity. Preexisting autoimmune diseases, such as rheumatoid arthritis, and biological treatments, like B cell depletion, are known to exhibit higher risk of severe COVID-19 manifestation and increased frequency of breakthrough infections after vaccination. We hypothesized that such increased risk is associated with an aberrant induction of secreted antibodies in the oral cavity.