A5064556073- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- interferon and immune responses
- Rheumatoid Arthritis Research and Therapies
- Nanoplatforms for cancer theranostics
- Carbohydrate Chemistry and Synthesis
- Redox biology and oxidative stress
- RNA modifications and cancer
- Atherosclerosis and Cardiovascular Diseases
- Influenza Virus Research Studies
- Adrenal Hormones and Disorders
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Vitamin D Research Studies
- Toxin Mechanisms and Immunotoxins
- Respiratory viral infections research
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Systemic Lupus Erythematosus Research
- Genomics and Chromatin Dynamics
Karolinska Institutet
2015-2025
Rockefeller University
2023
Abstract Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark rheumatoid arthritis (RA), the in vivo functions these remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their mice, as well specificities. None showed arthritogenicity nor induced pain-associated behavior mice. However, one antibodies, clone E4, protected mice antibody-induced arthritis. E4 binding pattern restricted to skin, macrophages...
Detailed characterization of cell type transitions is essential for biology in general and particularly the development stem cell-based therapies regenerative medicine. To systematically study such transitions, we introduce a method that simultaneously measures protein expression thermal stability changes cells provide web-based visualization tool ProteoTracker. We apply our to differences between human pluripotent several types including their parental line differentiated progeny. detect...
B cells undergo several rounds of selection to eliminate potentially pathogenic autoreactive clones, but in contrast T cells, evidence positive remains moot. Using unique tetramers, we traced natural (C1-B) specific for a defined triple-helical epitope on collagen type-II (COL2), constituting sizeable fraction the physiological cell repertoire mice, rats, and humans. Adoptive transfer C1-B suppressed arthritis independently IL10, separating them from IL10-secreting regulatory cells....
Significance Conclusive identification of single genes contributing to complex autoimmune diseases has been challenging. Here, we positionally identify the vitamin D3 receptor gene ( Vdr ) as a driver T cell-dependent inflammatory using forward genetics. In process, generated congenic mice that overexpress in cells consequence natural polymorphisms its promoter. These present unique opportunity study immunomodulatory properties VDR physiological setting. Moreover, restricted overexpression...
Abstract Complex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors probably controls the sex discrepancy in immune response, but underlying mechanisms unclear. Here we positionally identify a polymorphic estrogen receptor binding site that regulates Cd2 expression, leading to female-specific differences T cell-dependent mouse models of autoimmunity. Female mice with reduced expression have impaired autoreactive cell responses....
Pathogenic mutations in mitochondrial (mt) tRNA genes that compromise oxidative phosphorylation (OXPHOS) exhibit heteroplasmy and cause a range of multisyndromic conditions. Although disease patients are known to suffer from abnormal immune responses, how heteroplasmic mtDNA affect the system at molecular level is largely unknown. Here, mice carrying pathogenic C5024T mt-tRNAAla with encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) syndrome A3243G mt-tRNALeu, we found memory...
The control of chronic inflammation is dependent on the possibility limiting bystander activation autoreactive and potentially pathogenic T cells. We have identified a non-sense loss function single nucleotide polymorphism in C-type lectin receptor, Clec4b, shown that it controls autoimmune arthritis rat models rheumatoid arthritis. Clec4b specifically expressed CD4+ myeloid cells, mainly classical dendritic cells (DCs), defined by markers CD4+/MHCIIhi/CD11b/c+. found limited arthritogenic...
Abstract In this work, we have discovered that the Gal‐α‐(1→3)‐Gal‐β‐(1→3)‐GlcNAc trisaccharide, a fragment of B antigen Type‐1, is new ligand two C‐type lectin receptors (CLRs) i. e . DCAR and Mincle which are key players in different types autoimmune diseases. Accordingly, report here on straightforward methodology to access pure trisaccharide. A spacer with terminal primary amine group was included at reducing end GlcNAc residue thus ensuring further functionalization trisaccharide...
Animal models for complex diseases are needed to position and analyze the function of interacting genes. Previous positional cloning identified Ncf1 Clec4b be major regulators arthritis in rats. Here, we investigate epistasis between Clec4b, two We find that exert an additive effect on given by their joint ability regulate neutrophils. Both genes highly expressed neutrophils, together regulating neutrophil availability capacity generate reactive oxygen species. Using a glycan array, identify...
Abstract Pathogenic mitochondrial (mt)DNA molecules can exhibit heteroplasmy in single cells and cause a range of clinical phenotypes, although their contribution to immunity is poorly understood. Here, mice carrying heteroplasmic C5024T mt-tRNA Ala – that impairs oxidative phosphorylation we found reduced mutation burden peripheral T B memory lymphocyte subsets, compared naïve counterparts. Furthermore, selection diluting the was induced vitro by triggering cell antigen receptors. While...
Abstract Complex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors likely determines the sex discrepancy in immune response, but conclusive evidence is lacking regarding underlying molecular mechanisms. Using forward genetics, we positionally identified a polymorphic estrogen receptor binding site that regulates CD2 expression, leading to female-specific differences mouse models of T cell-dependent autoimmunity. Female mice with...