The intersection of COVID-19 and autoimmunity.

Acute COVID-19, caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Diseases Association Noel R.

Alterations in the spatiotemporal expression of the chemokine receptor CXCR4 in endothelial cells cause failure of hierarchical vascular branching.

The C-X-C chemokine receptor CXCR4 and its ligand CXCL12 play an important role in organ-specific vascular branching morphogenesis. CXCR4 is preferentially expressed by arterial endothelial cells, and local secretion of CXCL12 determines the organotypic pattern of CXCR4 arterial branching. Previous loss-of-function studies clearly demonstrated that CXCL12-CXCR4 signaling is necessary for proper arterial branching in the developing organs such as the skin and heart.

T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation.

IRF5 polymorphisms are associated with multiple immune-mediated diseases, including ulcerative colitis. IRF5 contributions are attributed to its role in myeloid lineages. How T cell-intrinsic IRF5 contributes to inflammatory outcomes is not well understood.

Integrated urine proteomics and renal single-cell genomics identify an IFN-γ response gradient in lupus nephritis.

Lupus nephritis, one of the most serious manifestations of systemic lupus erythematosus (SLE), has a heterogeneous clinical and pathological presentation. For example, proliferative nephritis identifies a more aggressive disease class that requires immunosuppression. However, the current classification system relies on the static appearance of histopathological morphology, which does not capture differences in the inflammatory response.

Publisher Correction: The immune cell landscape in kidneys of patients with lupus nephritis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Age and Other Risk Factors Influencing Long-Term Mortality in Patients With Traumatic Cervical Spine Fracture.

Objective: To identify clinical or demographic variables that influence long-term mortality, as well as in-hospital mortality, with a particular focus on the effects of age.

Summary And Background Data: Cervical spine fractures with or without spinal cord injury (SCI) disproportionately impact the elderly who constitute an increasing percentage of the US population.

Methods: We analyzed data collected for 10 years at a state-designated level I trauma center to identify variables that influenced in-hospital and long-term mortality among elderly patients with traumatic cervical spine fracture with or without SCI.

Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors.

Sepsis, a complex disorder characterized by immune, metabolic, and neurological dysregulation, is the number one killer in the intensive care unit. Mortality remains alarmingly high even in among discharged from the hospital. There is no clear strategy for managing this lethal chronic sepsis illness, which is associated with severe functional disabilities and cognitive deterioration.

Correlation of hypogammaglobulinaemia with proteinuria, and the relationship between hypogammaglobulinaemia and infection in active lupus nephritis.

Objective: To evaluate hypogammaglobulinaemia and risk of serious infectious adverse events in active lupus nephritis.

Methods: The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) compared abatacept with placebo in participants with lupus nephritis undergoing treatment with Euro-Lupus Nephritis low-dose cyclophosphamide. Serum IgG levels were assessed prior to initiation of treatment and throughout the trial.

Interferon regulatory factor 5 (IRF5) suppresses hepatitis C virus (HCV) replication and HCV-associated hepatocellular carcinoma.

Hepatitis C virus (HCV) infection is a major risk factor for the development of chronic liver disease. The disease typically progresses from chronic HCV to fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and death. Chronic inflammation associated with HCV infection is implicated in cirrhosis and HCC, but the molecular players and signaling pathways contributing to these processes remain largely unknown.

Unraveling Macrophage Heterogeneity in Erythroblastic Islands.

Mammalian erythropoiesis occurs within erythroblastic islands (EBIs), niches where maturing erythroblasts interact closely with a central macrophage. While it is generally accepted that EBI macrophages play an important role in erythropoiesis, thorough investigation of the mechanisms by which they support erythropoiesis is limited largely by inability to identify and isolate the specific macrophage sub-population that constitute the EBI. Early studies utilized immunohistochemistry or immunofluorescence to study EBI morphology and structure, while more recent efforts have used flow cytometry for high-throughput quantitative characterization of EBIs and their central macrophages.

A structural investigation of FISLE-412, a peptidomimetic compound derived from saquinavir that targets lupus autoantibodies.

FISLE-412 is the first reported small molecule peptidomimetic that neutralizes anti-dsDNA autoantibodies associated with systemic lupus erythematosus (SLE) pathogenesis. FISLE-412 is a complex small molecule that involves a challenging synthesis scheme, but has attractive pharmacological activities as a potential small molecule therapeutic in lupus. Therefore, we initiated a Structure-Activity Relationship study to simplify the complexity of FISLE-412.

Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets.

Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways.

Increased cathepsin S in Prdm1 dendritic cells alters the T cell repertoire and contributes to lupus.

Aberrant population expansion of follicular helper T cells (T cells) occurs in patients with lupus. An unanswered question is whether an altered repertoire of T cell antigen receptors (TCRs) is associated with such expansion. Here we found that the transcription factor Blimp-1 (encoded by Prdm1) repressed expression of the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves invariant chains and produces antigenic peptides for loading onto major histocompatibility complex (MHC) class II molecules.

Cocaine-induced splenic rupture.

Splenic rupture is a rare but serious complication from cocaine abuse. Given the ubiquitous prevalence of abuse and the potential for death from intraperitoneal bleeding, the prompt diagnosis and treatment of cocaine-induced disease including splenic rupture is essential. The management for splenic rupture from traumatic and atraumatic etiology has shifted from emergent laparotomy and splenectomy to non-operative approach with transcatheter splenic artery embolization.

Evidence for C1q-mediated crosslinking of CD33/LAIR-1 inhibitory immunoreceptors and biological control of CD33/LAIR-1 expression.

C1q collagen-like region (CLR) engaging and activating the LAIR-1 inhibitory immunoreceptor represents a non-complement mechanism for maintaining immune quiescence. Given the binding promiscuity of C1q's globular region (gC1q), we hypothesized that C1q concurrently associates with distinct inhibitory immunoreceptors to produce C1q-mediated modulatory networking. Like LAIR-1, CD33 inhibitory immunoreceptors are highly expressed on monocytes.

Interferon regulatory factor signaling in autoimmune disease.

Interferon regulatory factors (IRFs) play critical roles in pathogen-induced innate immune responses and the subsequent induction of adaptive immune response. Dysregulation of IRF signaling is therefore thought to contribute to autoimmune disease pathogenesis. Indeed, numerous murine in vivo studies have documented protection from or enhanced susceptibility to particular autoimmune diseases in Irf-deficient mice.

Kruppel-like factor4 regulates expression through binding to an autoimmune risk allele.

A SNP identified as rs548234, which is found in , the gene that encodes BLIMP1, is a risk allele associated with systemic lupus erythematosus (SLE). BLIMP1 expression was reported to be decreased in women with the rs548234 risk allele compared with women with the nonrisk allele in monocyte-derived DCs (MO-DCs). In this study, we demonstrate that BLIMP1 expression is regulated by the binding of Kruppel-like factor 4 (KLF4) to the risk SNP.

Immune-mediated brain pathology: from autoantibodies to microglia.

Cells and molecules of the immune system contribute to brain pathology as well as to brain homeostasis. We suggest that there are numerous anti-brain antibodies that can cause acute neuronal dysfunction if they penetrate brain parenchyma. Many of these acute immune-mediated insults may alter the homeostatic mechanisms in the brain and initiate pathologic events that no longer depend on the presence of the inciting antibody, but rather on microglial cell activation.

C1q and HMGB1 reciprocally regulate human macrophage polarization.

A healthy immune system results from a balance of stimulatory and inhibitory pathways that allow effective responses to acute insults, without descending into chronic inflammation. Failed homeostasis is characteristic of autoimmune diseases such as systemic lupus erythematosus. Although HMGB1 induces proinflammatory M1-like macrophage differentiation, we describe a mechanism by which C1q modulates this activity and collaborates with HMGB1 to induce the differentiation of monocytes to anti-inflammatory M2-like macrophages.

Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice.

Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting males. It encompasses a group of neurodevelopmental abnormalities characterized by impaired social interaction and communication, stereotypic behaviors and motor dysfunction. Although recent advances implicate maternal brain-reactive antibodies in a causative role in ASD, a definitive assessment of their pathogenic potential requires cloning of such antibodies.

Blood pressure regulation by CD4 lymphocytes expressing choline acetyltransferase.

Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4 T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals. Here we show that these CD4CD44CD62L T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T).

DNA-reactive B cells in lupus.

IgG anti-DNA antibodies are both diagnostic and pathogenic for systemic lupus erythematosus (SLE). They contribute to tissue inflammation through direct tissue binding and to systemic inflammation through activation of Toll-like receptors by nucleic acid-containing immune complexes. IgG DNA-reactive antibodies originate when B cell tolerance mechanisms are impaired.

Specific detection of interferon regulatory factor 5 (IRF5): A case of antibody inequality.

Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors. IRF5 was first identified and characterized as a transcriptional regulator of type I interferon expression after virus infection. In addition to its critical role(s) in the regulation and development of host immunity, subsequent studies revealed important roles for IRF5 in autoimmunity, cancer, obesity, pain, cardiovascular disease, and metabolism.