Genetic variants that helped the immune system fight the Black Death may have had the side effect of increasing susceptibility to autoimmune diseases.
RCCX Genetic Module Theory
NOTE: This page is modified from a summary of findings available at the RCCX and Illness website.
The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases
The interaction disorder between gut microbiota and its host has been documented in different non-communicable diseases (NCDs) such as metabolic syndrome, neurodegenerative disease, and autoimmune ...
The mycobiota: interactions between commensal fungi and the host immune system
The fungal microbiota, or 'mycobiota', is an understudied component of the microflora that is found on all mucosal surfaces and on the skin.Like other microorganisms, fungi interact with the immune system at these surfaces in ways that are important both for host defence and for regulating the immune system.Investigators who study the mycobiota face both biological and bioinformatic challenges.The study of human genetic disorders and genetic polymorphisms teaches us about the mechanisms by which commensal and pathogenic fungi interact with the immune system.
Accurate and scalable multi-disease classification from adaptive immune repertoires
Summary BackgroundMachine learning models trained on paratope-similarity networks have shown superior accuracy compared with clonotype-based models in binary disease classification. However, the computational demands of paratope networks hinder their use on large datasets and multi-disease classification.MethodsWe reanalyzed publicly available T cell receptor (TCR) repertoire data from 1,421 donors across 15 disease groups and a large control group, encompassing approximately 81 million TCR sequences.
Mucosal dendritic cells shape mucosal immunity
Dendritic cells (DCs) are key modulators that shape the immune system. In mucosal tissues, DCs act as surveillance systems to sense infection and also function as professional antigen-presenting cells that stimulate the differentiation of naive T and B cells. On the basis of their molecular expression, DCs can be divided into several subsets with unique functions. In this review, we focus on intestinal DC subsets and their function in bridging the innate signaling and adaptive immune systems to maintain the homeostasis of the intestinal immune environment. We also review the current strategies for manipulating mucosal DCs for the development of efficient mucosal vaccines to protect against infectious diseases.
<p>The Rising Era of “Immunoporosis”: Role of Immune System in the Pathophysiology of Osteoporosis</p>
We exhaustively revisit the characteristics, mechanism of action, and function of both innate and adaptive immune cells .
Immunoporosis: Immunology of Osteoporosis—Role of T Cells
The role of immune system in various bone pathologies such as osteoporosis, osteoarthritis and rheumatoid arthritis is now well established. This had led to the emergence of a modern field of systems biology called as osteoimmunology, an integrated research between fields of immunology and bone biology under one umbrella. Osteoporosis is one of the most common inflammatory bone-loss conditions with more than 200 million individuals affected worldwide. T helper cells along with various other immune cells are major players involved in bone homeostasis. In the present review, we specifically discuss the role of various defined T lymphocyte subsets (Th cells comprising Th1, Th2, Th9, Th17, Th22, regulatory T cells, follicular helper T cells, natural killer T cells, γδ T cells and CD8+ T cells) in the pathophysiology of osteoporosis. The study of the specific role of immune system in osteoporosis has now been proposed by our group as “Immunoporosis: The immunology of osteoporosis” with special emphasis on the role of various subsets of T lymphocytes. The establishment of this new field had been the need of the hour due to the emergence of novel roles of various T cell lymphocytes in accelerated bone loss observed during osteoporosis. Activated T cells either directly or indirectly through the secretion of various cytokines and factors modulate bone health and thereby regulate bone remodelling. Various studies have summarized the role of inflammation in pathogenesis of osteoporosis, but very few reports had delineated the precise role of various T cell subsets in the pathobiology of osteoporosis. The present review thus for the first time clearly highlights and summarizes the role of various T lymphocytes in the development and pathophysiology of osteoporosis, giving birth to a new field of biology termed as “Immunoporosis”. This novel field will thus provide an overview of the nexus between the cellular components of both bone and immune systems, responsible for the observed bone loss in osteoporosis. A molecular insight into the upcoming and novel field of immunoporosis would thus lead to development of innovative approaches for the prevention and treatment of osteoporosis.
OSTEOIMMUNOLOGY: Interplay Between the Immune System and Bone Metabolism
Studies of bone and the immune system have converged in recent years under the banner of osteoimmunology. The immune system is spawned in the bone marrow reservoir, and investigators now recognize that important niches also exist there for memory lymphocytes. At the same time, various factors produced during immune responses are capable of profoundly affecting regulation of bone. Mechanisms have evolved to prevent excessive interference by the immune system with bone homeostasis, yet pathologic bone loss is a common sequela associated with autoimmunity and cancer. There are also developmental links, or parallels, between bone and the immune system. Cells that regulate bone turnover share a common precursor with inflammatory immune cells and may restrict themselves anatomically, in part by utilizing a signaling network analogous to lymphocyte costimulation. Efforts are currently under way to further characterize how these two organ systems overlap and to develop therapeutic strategies that benefit from this understanding.
Finding Exercise Balance with Autoimmune Diseases
Evidence mounts that Long Covid is damaging the hearts of those affected
There are also increasing signs that the condition can disrupt the autonomic nervous system
LLM-Assisted Reanalysis of Unsolved Rare Disease Genomes Increases Diagnostic Yield
Rare and undiagnosed genetic disorders affect millions of patients globally, and many patients endure years of inconclusive testing. Conventional genomic interpretation can be insufficiently sensit...
Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation
Matatall et al. show that chronic infection causes pancytopenia and hematopoietic stem cell (HSC) depletion in mice. HSCs are lost through impaired self-renewal and increased terminal differentiation, which can be triggered by induction of the interferon gamma-responsive transcription factor BATF2. This study elucidates mechanisms underlying bone marrow failure during chronic infections.
Osteopetrosis in mice lacking NF-κB1 and NF-κB2
The nfkbl and nfkb2 genes encode closely related products regulating immune and inflammatory responses1–3. Their role during development and differentiation remains unclear. The generation of nfkb1 null mice (p50−/−) resulted in altered immune responses, but had no effect on development4. Similarly, nfkb2 knockout mice (p52−/−) did not show developmental defects (J.C. et al., manuscript submitted). We have investigated the potential for in vivo compensatory functions of these genes by generating double-knockout mice. The surprising result was that the animals developed osteopetrosis because of a defect in osteoclast differentiation, suggesting redundant functions of NF-κB1 and NF-κB2 proteins in the development of this cell lineage. The osteopetrotic phenotype was rescued by bone marrow transplantation, indicating that the hematopoietic component was impaired. These results define a new mouse osteopetrotic mutant and implicate NF-κB proteins in bone development, raising new directions in the treatment of bone disorders.
Ebola outbreak caused by new ‘animal transmission’: What that means
More than 2,000 people have died after contracting the latest strain of the Ebola virus.
Mathematical Discovery of Potential Therapeutic Targets: Application to Rare Melanomas
Patients with rare types of melanoma such as acral, mucosal, or uveal melanoma, have lower survival rates than patients with cutaneous melanoma; these lower survival rates reflect the lower objective response rates to immunotherapy compared to cutaneous melanoma. Understanding tumor-immune dynamics in rare melanomas is critical for the development of new therapies and for improving response rates to current cancer therapies. Progress has been hindered by the lack of clinical data and the need for better preclinical models of rare melanomas. Canine melanoma provides a valuable comparative oncology model for rare types of human melanomas. We analyzed RNA sequencing data from canine melanoma patients and combined this with literature information to create a novel mechanistic mathematical model of melanoma-immune dynamics. Sensitivity analysis of the mathematical model indicated influential pathways in the dynamics, providing support for potential new therapeutic targets and future combinations of therapies. We share our learnings from this work, to help enable the application of this proof-of-concept workflow to other rare disease settings with sparse available data.
Immunoporosis: Role of Innate Immune Cells in Osteoporosis
Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as ‘bone remodeling’. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term “immunoporosis” to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPS), damage-associated molecular patterns (DAMPS), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.
