C-reactive protein orchestrates acute allograft rejection in vascularized composite allotransplantation via selective activation of monocyte subsets.

Introduction: Despite advancements in transplant immunology and vascularized composite allotransplantation (VCA), the longevity of allografts remains hindered by the challenge of allograft rejection. The acute-phase response, an immune-inflammatory reaction to ischemia/reperfusion that occurs directly after allogeneic transplantation, serves as a catalyst for graft rejection. This immune response is orchestrated by acute-phase reactants through intricate crosstalk with the mononuclear phagocyte system.

Burden of disease and impact on quality of life in chronic back pain - a comparative cross-sectional study of 150 axial spondyloarthritis and 150 orthopedic back pain patients.

Objective: Chronic back pain (CBP) constitutes one of the most common complaints in primary care and a leading cause of disability worldwide. CBP may be of mechanical or inflammatory character and may lead to functional impairment and reduced quality of life. In this study, we aimed to assess and compare burden of disease, functional capacity, quality of life and depressive symptoms in axial spondyloarthritis (axSpA) patients with orthopedic chronic back pain patients (OBP).

Impact of dietary vitamin D on immunoregulation and disease pathology in lupus-prone NZB/W F1 mice.

Vitamin D (VD) deficiency is a highly prevalent worldwide phenomenon and is extensively discussed as a risk factor for the development of systemic lupus erythematosus (SLE) and other immune-mediated diseases. In addition, it is now appreciated that VD possesses multiple immunomodulatory effects. This study aims to explore the impact of dietary VD intake on lupus manifestation and pathology in lupus-prone NZB/W F1 mice and identify the underlying immunological mechanisms modulated by VD.

Low-Salt Diet Attenuates B-Cell- and Myeloid-Cell-Driven Experimental Arthritides by Affecting Innate as Well as Adaptive Immune Mechanisms.

A link between high sodium chloride (salt) intake and the development of autoimmune diseases was previously reported. These earlier studies demonstrated exacerbation of experimental autoimmune encephalomyelitis and colitis by excess salt intake associated with Th17- and macrophage-mediated mechanisms. Little is known about the impact of dietary salt intake on experimental arthritides.

Detection and functional resolution of soluble immune complexes by an FcγR reporter cell panel.

Fc-gamma receptor (FcγR) activation by soluble IgG immune complexes (sICs) represents a major mechanism of inflammation in certain autoimmune diseases such as systemic lupus erythematosus (SLE). A robust and scalable test system allowing for the detection and quantification of sIC bioactivity is missing. We developed a comprehensive reporter cell panel detecting activation of FcγRs.

Low Dietary Fiber Intake Links Development of Obesity and Lupus Pathogenesis.

Changed dietary habits in Western countries such as reduced fiber intake represent an important lifestyle factor contributing to the increase in inflammatory immune-mediated diseases. The mode of action of beneficial fiber effects is not fully elucidated, but short-chain fatty acids (SCFA) and gut microbiota have been implicated. The aim of this study was to explore the impact of dietary fiber on lupus pathology and to understand underlying mechanisms.

CMTM6-Deficient Monocytes in ANCA-Associated Vasculitis Fail to Present the Immune Checkpoint PD-L1.

Objectives: ANCA-associated vasculitides (AAV) affect small- and medium-sized blood vessels. In active disease, vessel wall infiltrates are mainly composed of monocytes and macrophages. Immune checkpoint molecules are crucial for the maintenance of self-tolerance and the prevention of autoimmune diseases.

Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus.

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus.

Relevance of Receptor for Advanced Glycation end Products (RAGE) in Murine Antibody-Mediated Autoimmune Diseases.

It is incompletely understood how self-antigens become targets of humoral immunity in antibody-mediated autoimmune diseases. In this context, alarmins are discussed as an important level of regulation. Alarmins are recognized by various receptors, such as receptor for advanced glycation end products (RAGE).

Optimized isolation of renal plasma cells for flow cytometric analysis.

Plasma cells (PCs) secrete antibodies and play an essential role in protective immunity, but also in pathogenesis of antibody-mediated diseases. Physiologically, PCs mainly reside within bone marrow and spleen. In autoimmune diseases such as systemic lupus erythematosus (SLE) autoantibody-producing PCs can also be found at sites of inflammation, e.

Avenues to autoimmune arthritis triggered by diverse remote inflammatory challenges.

Environmental factors contribute to development of autoimmune diseases. For instance, human autoimmune arthritis can associate with intestinal inflammation, cigarette smoking, periodontal disease, and various infections. The cellular and, molecular pathways whereby such remote challenges might precipitate arthritis or flares remain unclear.

Analysis of dendritic cell subpopulations in follicular lymphoma with respect to the tumor immune microenvironment.

The immune cell composition of the follicular lymphoma (FL) tumor microenvironment is increasingly recognized as an important determinant for clinical outcome. Here, we explored frequency and distribution of dendritic cell (DC) subtypes in relation to regulatory T cells (Treg) by immunohistochemistry in lymph node biopsies from patients with de novo FL. We found that neoplastic follicles contained lower DC and higher Treg frequencies than hyperplastic follicles in control lymph nodes.

The Role of Follicular Helper T Cell Molecules and Environmental Influences in Autoantibody Production and Progression to Inflammatory Arthritis in Mice.

Objective: Antibody-mediated autoimmunity involves cognate interactions between self-reactive T cells and B cells during germinal center (GC) reactions. The aim of this study was to determine the role of essential follicular helper T (Tfh) cell molecules (CXCR5, signaling lymphocytic activation molecule-associated protein) on autoreactive CD4+ cells and the role of certain environmental influences that may determine GC-driven autoantibody production and arthritis development.

Methods: We transferred self-reactive CD4+ cells from KRN-Tg mice into recipient mice, which induced autoantibodies and autoinflammatory arthritis.

Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites.

Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function.

Quantifying helper cell function of human TFH cells in vitro.

Blood-circulating CXCR5(+) CD4(+) T cells and T follicular helper (TFH) cells, which participate in germinal center (GC) reactions within secondary lymphoid organs, are specialized in providing help to B cells. This chapter describes ways to isolate TFH-like cells out of peripheral blood or tonsils and to quantify their B cell helper function. This comprises different co-culture approaches of TFH-like cells and B cells and the evaluation of their capacity to induce immunoglobulin secretion and plasma cell differentiation.

Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome.

Diet and the gut microbiota may underpin numerous human diseases. A major metabolic product of commensal bacteria are short-chain fatty acids (SCFAs) that derive from fermentation of dietary fibre. Here we show that diets deficient or low in fibre exacerbate colitis development, while very high intake of dietary fibre or the SCFA acetate protects against colitis.

Inflammation and lymphopenia trigger autoimmunity by suppression of IL-2-controlled regulatory T cell and increase of IL-21-mediated effector T cell expansion.

The dynamic interplay between regulatory T cells (T(regs)) and effector T cells (T(effs)) governs the balance between tolerance and effector immune responses. Perturbations of T(reg) frequency and function or imbalances in T(reg)/T(eff) levels are associated with the development of autoimmunity. The factors that mediate these changes remain poorly understood and were investigated in this study in murine autoimmune arthritis.

Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.

Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases.

Pneumococcal components induce regulatory T cells that attenuate the development of allergic airways disease by deviating and suppressing the immune response to allergen.

The induction of regulatory T cells (Tregs) to suppress aberrant inflammation and immunity has potential as a therapeutic strategy for asthma. Recently, we identified key immunoregulatory components of Streptococcus pneumoniae, type 3 polysaccharide and pneumolysoid (T+P), which suppress allergic airways disease (AAD) in mouse models of asthma. To elucidate the mechanisms of suppression, we have now performed a thorough examination of the role of Tregs.

CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses.

High expression of CXCR5 is one of the defining hallmarks of T follicular helper cells (T(FH)), a CD4 Th cell subset that promotes germinal center reactions and the selection and affinity maturation of B cells. CXCR5 is also expressed on 20-25% of peripheral blood human central memory CD4 T cells (T(CM)), although the definitive function of these cells is not fully understood. The constitutive expression of CXCR5 on T(FH) cells and a fraction of circulating T(CM) suggests that CXCR5(+) T(CM) may represent a specialized subset of memory-type T(FH) cells programmed for homing to follicles and providing B cell help.

Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia.

B-cell receptor signaling contributes to apoptosis resistance in chronic lymphocytic leukemia (CLL), limiting the efficacy of current therapeutic approaches. In this study, we investigated the expression of spleen tyrosine kinase (SYK), a key component of the B-cell receptor signaling pathway, in CLL and its role in apoptosis. Gene expression profiling identified enhanced expression of SYK and downstream pathways in CLL compared with healthy B cells.

Membrane targeting of a bacterial virulence factor harbouring an extended signal peptide.

Filamentous haemagglutinin (FHA) is the major adhesin of Bordetella pertussis, the whooping cough agent. FHA is synthesized as a 367-kDa precursor harbouring a remarkably long signal peptide with an N-terminal extension that is conserved among related virulence proteins. FHA is secreted via the two-partner secretion pathway that involves transport across the outer membrane by a cognate transporter protein.