The clinical features and potential mechanisms of cognitive disorders in peripheral autoimmune and inflammatory diseases

According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders 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,autoantibodies 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.

Ubiquitination modification:critical regulation of IRF family stability and activity

Interferon regulatory factors(IRFs)play pivotal and critical roles in innate and adaptive immune responses;thus,precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary.The stability and activities of IRFs are directly or indirectly targeted by endogenous and exogenous proteins in an ubiquitin-dependent manner.However,few reviews have summarized how host E3 ligases/DUBs or viral proteins regulate IRF stability and activity.Additionally,with recent technological developments,details about the ubiquitination of IRFs have been continuously revealed.As knowledge of how these proteins function and interact with IRFs may facilitate a better understanding of the regulation of IRFs in immune responses or other biological processes,we summarized current studies on the direct ubiquitination of IRFs,with an emphasis on how these proteins interact with IRFs and affect their activities,which may provide exciting targets for drug development by regulating the functions of specific E3 ligases.

The essential functions of mitochondrial dynamics in immune cells

Mitochondria are highly mobile organelles due to fission,fusion,transport,and mitophagy,and these processes are known as mitochondrial dynamics.Mitochondrial dynamics play an important role in energy production,cell division,cell differentiation,and cell death.In the past decade,numerous studies have revealed the importance of mitochondrial metabolism in immunity,and mitochondrial dynamics are essential for immune responses mediated by various cell types.In this review,we mainly discuss the role of mitochondrial dynamics in activation,differentiation,cytokine production,and the activity of related pathways in immune cells,particularly T cells,B cells,and other cells involved in the innate immune response.

A double-edged sword of immuno-microenvironment in cardiac homeostasis and injury repair

The response of immune cells in cardiac injury is divided into three continuous phases:inflammation,proliferation and maturation.The kinetics of the inflammatory and proliferation phases directly influence the tissue repair.In cardiac homeostasis,cardiac tissue resident macrophages(cTMs)phagocytose bacteria and apoptotic cells.Meanwhile,NK cells prevent the maturation and transport of inflammatory cells.After cardiac injury,cTMs phagocytose the dead cardiomyocytes(CMs),regulate the proliferation and angiogenesis of cardiac progenitor cells.NK cells prevent the cardiac fibrosis,and promote vascularization and angiogenesis.Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage.Reversely,type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage.Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines,and then release anti-inflammatory cytokines and growth factors,which regulate cardiac remodeling.In this process,dendritic cells(DCs)mediate the regulation of monocyte and macrophage recruitment.Recruited eosinophils and Mast cells(MCs)release some mediators which contribute to coronary vasoconstriction,leukocyte recruitment,formation of new blood vessels,scar formation.In adaptive immunity,effector T cells,especially Th17 cells,lead to the pathogenesis of cardiac fibrosis,including the distal fibrosis and scar formation.CMs protectors,Treg cells,inhibit reduce the inflammatory response,then directly trigger the regeneration of local progenitor cell via IL-10.B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.