Podoplanin expressing macrophages and their involvement in tertiary lymphoid structures in mouse models of Sjögren's disease.

Tertiary lymphoid structures (TLSs) are formed in tissues targeted by chronic inflammation processes, such as infection and autoimmunity. In Sjögren's disease, the organization of immune cells into TLS is an important part of disease progression. Here, we investigated the dynamics of tissue resident macrophages in the induction and expansion of salivary gland TLS.

Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus.

There are several autoimmune and rheumatic diseases affecting different organs of the human body. Multiple sclerosis (MS) mainly affects brain, rheumatoid arthritis (RA) mainly affects joints, Type 1 diabetes (T1D) mainly affects pancreas, Sjogren's syndrome (SS) mainly affects salivary glands, while systemic lupus erythematosus (SLE) affects almost every organ of the body. Autoimmune diseases are characterized by production of autoantibodies, activation of immune cells, increased expression of pro-inflammatory cytokines, and activation of type I interferons.

Chip-based multimodal super-resolution microscopy for histological investigations of cryopreserved tissue sections.

Histology involves the observation of structural features in tissues using a microscope. While diffraction-limited optical microscopes are commonly used in histological investigations, their resolving capabilities are insufficient to visualize details at subcellular level. Although a novel set of super-resolution optical microscopy techniques can fulfill the resolution demands in such cases, the system complexity, high operating cost, lack of multi-modality, and low-throughput imaging of these methods limit their wide adoption for histological analysis.

Interplay of immune and kidney resident cells in the formation of tertiary lymphoid structures in lupus nephritis.

Kidney involvement confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis (LN) involves diverse mechanisms instigated by elements of the autoimmune response which alter the biology of kidney resident cells. Processes in the glomeruli and in the interstitium may proceed independently albeit crosstalk between the two is inevitable.

Kidney Tertiary Lymphoid Structures in Lupus Nephritis Develop into Large Interconnected Networks and Resemble Lymph Nodes in Gene Signature.

Immune aggregates organized as tertiary lymphoid structures (TLS) are observed within the kidneys of patients with systemic lupus erythematosus and lupus nephritis (LN). Renal TLS was characterized in lupus-prone New Zealand black × New Zealand white F1 mice analyzing cell composition and vessel formation. RNA sequencing was performed on transcriptomes isolated from lymph nodes, macrodissected TLS from kidneys, and total kidneys of mice at different disease stages by using a personal genome machine and RNA sequencing.

LMW heparin prevents increased kidney expression of proinflammatory mediators in (NZBxNZW)F1 mice.

We have previously demonstrated that continuous infusion of low molecular weight (LMW) heparin delays autoantibody production and development of lupus nephritis in (NZBxNZW)F1 (B/W) mice. In this study we investigated the effect of LMW heparin on renal cytokine and chemokine expression and on nucleosome-mediated activation of nucleosome-specific splenocytes. Total mRNA extracted from kidneys of heparin-treated or -untreated B/W mice was analysed by qPCR for the expression of several cytokines, chemokines, and Toll-like receptors.

Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice.

The glomerular targets for nephritogenic antibodies have been identified as membrane-associated chromatin fragments. The processes responsible for their deposition are poorly understood. To determine early events in antibody-mediated nephritis, we injected highly pure anti-dsDNA mAbs into BALB/c mice.

Renal expression of polyomavirus large T antigen is associated with nephritis in human systemic lupus erythematosus.

We have demonstrated that glomerular expression of polyomavirus large T antigen (T-ag) in a binary tetracycline-regulated T-ag transgenic mouse model (i) terminated tolerance for nucleosomes, (ii) released complexes of nucleosomes and T-ag to the microenvironment from dead cells, and (iii) that these complexes bound induced anti-nucleosome antibodies and finally (iv) that they associated with glomerular membranes as immune complexes. This process may be relevant for human lupus nephritis, since productive polyomavirus infection is associated with this organ manifestation. Here, we compare nephritis in the T-ag transgenic mouse with nephritis in human SLE.