查看更多>>摘要：The pancreas exerts endocrine and exocrine functions in energy balance.The neural innervation and immune mi-lieu are both crucial in supporting pancreatic homeostasis.The neuronal network connects the pancreas with the central nervous system(CNS)and the enteric nervous system(ENS)and sustains metabolic activities.The nerves in the pancreas are categorized as spinal sensory afferent fibers,vagal sensory afferent nerves,autonomic fibers of both sympathetic and parasympathetic divisions,and fibers from the ENS and intrapancreatic ganglia.They innervate different regions and various cell types,which collectively determine physiological functions.Studies have established that the diverse pathological conditions,including pancreatitis,diabetes,and pancreatic tumor,are attributed to aberrant immune reactions;however,it is largely not clear how the neuronal network may influence the disease conditions.Enlightened by the recent advances illuminating the organ-wide neuronal archi-tecture and the dysfunctions in pancreatic disorders,this review will highlight emerging opportunities to explore the cellular interrelationship,particularly the neuroimmune components in pancreatic health and diseases.
查看更多>>摘要：Neuroimmunology is an interdisciplinary branch of biomedical science that emerges from the intersection of studies on the nervous system and the immune system.The complex interplay between the two systems has long been recognized.Research efforts directed at the underlying functional interface and associated patho-physiology,however,have garnered attention only in recent decades.In this narrative review,we highlight significant advances in research on neuroimmune interplay and modulation.A particular focus is on early-and middle-career neuroimmunologists in China and their achievements in frontier areas of"neuroimmune inter-face","neuro-endocrine-immune network and modulation","neuroimmune interactions in diseases","meningeal lymphatic and glymphatic systems in health and disease",and"tools and methodologies in neuroimmunology re-search".Key scientific questions and future directions for potential breakthroughs in neuroimmunology research are proposed.
查看更多>>摘要：Skin is a vital barrier tissue of the body.Immune responses in the skin must be precisely controlled,which would otherwise cause severe disease conditions such as psoriasis,atopic dermatitis,or pathogenic infection.Research evidence has increasingly demonstrated the essential roles of neural innervations,i.e.,sensory and sympathetic signals,in modulating skin immunity.Notably,neuropathic changes of such neural structures have been observed in skin disease conditions,implicating their direct involvement in various pathological processes.An in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic interventions.Here,we summarize the neuroimmune interactions between neuropathic events and skin immunity,highlighting the current knowledge and future perspectives of this emerging research frontier.
查看更多>>摘要：According to a study from World Health Organization's Global Burden of Disease,mental and neurological disor-ders have accounted for 13％ of global diseases in recent years and are on the rise.Neuropsychiatric conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system(CNS).Cognitive dysfunction(CD)encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases,especially in multiple non-CNS-related autoimmune diseases.Recent studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases,including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier(BBB)to trigger a central neuroinflammatory response.When the BBB is intact,au-toantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia,inducing CNS inflammation and CD.However,the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are uncertain.In this review,we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS,summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment,and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology.
查看更多>>摘要：Microglia are resident immune cells in the central nervous system(CNS)that play vital roles in CNS development,homeostasis and disease pathogenesis.Genetic defects in microglia lead to microglial dysfunction,which in turn leads to neurological disorders.The correction of the specific genetic defects in microglia in these disorders can lead to therapeutic effects.Traditional genetic defect correction approaches are dependent on viral vector-based genetic defect corrections.However,the viruses used in these approaches,including adeno-associated viruses,lentiviruses and retroviruses,do not primarily target microglia;therefore,viral vector-based genetic defect corrections are ineffective in microglia.Microglia replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy microglia.In this paper,we systematically review the history,rationale and therapeutic perspectives of microglia replacement,which would be a novel strategy for treating CNS disorders.
查看更多>>摘要：Emerging evidence has highlighted the capacity of hematogenous cells in skull and vertebral bone marrow to enter the meningeal borders via ossified vascular channels and maintain immune homeostasis in the central nervous system(CNS).CNS-adjacent skull and vertebral bone marrow comprises hematopoietic niches that can sense CNS injury and supply specialized immune cells to fine-tune inflammatory responses.Here,we review recent advances in our understanding of skull and vertebral bone marrow-derived immune cells in homeostasis and inflammatory CNS diseases.Further,we discuss the implications for future development of therapies to mitigate CNS inflammation and its detrimental sequelae in neurological disorders.
查看更多>>摘要：The nervous system possesses bidirectional,sophisticated and delicate communications with the immune system.These neuroimmune interactions play a vitally important role in the initiation and development of many disorders,especially neurodegenerative diseases.Although scientific advancements have made tremendous progress in this field during the last few years,neuroimmune communications are still far from being elucidated.By organizing recent research,in this review,we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis.It will also facilitate a view of the diseases from a holistic,pluralistic and interconnected perspective,thus providing a basis of developing novel and effective methods to diagnose,intervene and treat diseases.
查看更多>>摘要：Fibroblasts are typically described as cells that produce extracellular matrix,contribute to the formation of con-nective tissue,and maintain the structural framework of tissues.Fibroblasts are the first cell type to be transdif-ferentiated into inducible pluripotent stem cells(iPSCs),demonstrating their versatility and reprogrammability.Currently,there is relatively extensive characterization of the anatomical,molecular,and functional diversity of fibroblasts in different peripheral organs and tissues.With recent advances in single cell RNA sequencing,heterogeneity and diversity of fibroblasts in the central nervous system(CNS)have also begun to emerge.Based on their distinct anatomical locations in the meninges,perivascular space,and choroid plexus,as well as their molecular diversity,important roles for fibroblasts in the CNS have been proposed.Here,we draw inspirations from what is known about fibroblasts in peripheral tissues,in combination with their currently identified CNS locations and molecular characterizations,to propose potential functions of CNS fibroblasts in health and disease.Future studies,using a combination of technologies,will be needed to determine the bona fide in vivo functions of fibroblasts in the CNS.
查看更多>>摘要：Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies includ-ing surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of var-ious CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.
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