Regulation of neuroimmune processes by damage-and resolution-associated molecular patterns

Sterile inflammatory processes are essential for the maintenance of central nervous system homeostasis,but they also contribute to various neurological disorders,including neurotrauma,stroke,and demyelinating or neurodegenerative diseases.Immune mechanisms in the central nervous system and periphery are regulated by a diverse group of endogenous proteins,which can be broadly divided into the pro-inflammatory damageassociated molecular patterns(DAMPs)and anti-inflammatory resolution-associated molecular patterns(RAMPs),even though there is notable overlap between the DAMPand RAMP-like activities for some of these molecules.Both groups of molecular patterns were initially described in peripheral immune processes and pathologies;however,it is now evident that at least some,if not all,of these immunomodulators also regulate neuroimmune processes and contribute to neuroinflammation in diverse central nervous system disorders.The review of recent literature demonstrates that studies on DAMPs and RAMPs of the central nervous system still lag behind the much broader research effort focused on their peripheral counterparts.Nevertheless,this review also reveals that over the last five years,significant advances have been made in our understanding of the neuroimmune functions of several well-established DAMPs,including high-mobility group box 1 protein and interleukin 33.Novel neuroimmune functions have been demonstrated for other DAMPs that previously were considered almost exclusively as peripheral immune regulators;they include mitochondrial transcription factor A and cytochrome C.RAMPs of the central nervous system are an emerging area of neuroimmunology with very high translational potential since some of these molecules have already been used in preclinical and clinical studies as candidate therapeutic agents for inflammatory conditions,such as multiple sclerosis and rheumatoid arthritis.The therapeutic potential of DAMP antagonists and neutralizing antibodies in central nervous system neuroinflammatory diseases is also supported by several of the identified studies.It can be concluded that further studies of DAMPs and RAMPs of the central nervous system will continue to be an important and productive field of neuroimmunology.

Responses of Hodgkin-Huxley Neuronal Systems to Spike-Train Inputs

We investigate responses of the Hodgkin-Huxley globally neuronal systems to periodic spike-train inputs. The firing activities of the neuronal networks show different rhythmic patterns for different parameters. These rhyth- mic patterns can be used to explain cycles of firing in real brain. These activity patterns, average activity and coherence measure are affected by two quantities such as the percentage of excitatory couplings and stimulus intensity, in which the percentage of excitatory couplings is more important than stimulus intensity since the transition phenomenon of average activity comes about.

A pair of G-type lectin receptor-like kinases modulates nlp20-mediated immune responses by coupling to the RLP23 receptor complex

Plant cells recognize microbial patterns with the plasma-membrane-localized pattern-recognition receptors consisting mainly of receptor kinases(RKs) and receptor-like proteins(RLPs). RKs, such as bacterial flagellin receptor FLS2, and their downstream signaling components have been studied extensively. However, newly discovered regulatory components of RLP-mediated immune signaling, such as the nlp20 receptor RLP23, await identification. Unlike RKs, RLPs lack a cytoplasmic kinase domain, instead recruiting the receptor-like kinases(RLKs) BAK1 and SOBIR1. SOBIR1 specifically works as an adapter for RLP-mediated immunity. To identify new regulators of RLP-mediated signaling, we looked for SOBIR1-binding proteins(SBPs) in Arabidopsis thaliana using protein immunoprecipitation and mass spectrometry,identifying two G-type lectin RLKs, SBP1 and SBP2, that physically interacted with SOBIR1.SBP1 and SBP2 showed high sequence similarity,were tandemly repeated on chromosome 4, and also interacted with both RLP23 and BAK1. sbp1 sbp2 double mutants obtained via CRISPR-Cas9 gene editing showed severely impaired nlp20-induced reactive oxygen species burst, mitogenactivated protein kinase(MAPK) activation, and defense gene expression, but normal flg22-induced immune responses. We showed that SBP1 regulated nlp20-induced immunity in a kinase activityindependent manner. Furthermore, the nlp20-induced the RLP23–BAK1 interaction, although not the flg22-induced FLS2–BAK1 interaction, was significantly reduced in sbp1 sbp2. This study identified SBPs as new regulatory components in RLP23 receptor complex that may specifically modulate RLP23-mediated immunity by positively regulating the interaction between the RLP23 receptor and the BAK1 co-receptor.

Cellular and molecular regulation of innate inflammatory responses

Innate sensing of pathogens by pattern-recognition receptors （PRRs） plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inflammatory responses. The initiation, activation and resolution of innate inflammatory response are mediated by a complex network of interactions among the numerous cellular and molecular components of immune and non- immune system. While a controlled and beneficial innate inflammatory response is critical for the elimination of pathogens and maintenance of tissue homeostasis, dysregulated or sustained inflammation leads to pathological conditions such as chronic infection, inflammatory autoimmune diseases. In this review, we discuss some of the recent advances in our understanding of the cellular and molecular mechanisms for the establishment and reJzulation of innate immunity and inflammatory responses.

An overview of inflammation: mechanism and consequences

Inflammation is an essential response provided by the immune systems that ensures the survival duringinfection and tissue injury. Inflammatory responses are essential for the maintenance of normal tissue homeostasis. Themolecular mechanism of inflammation is quite a complicated process which is initiated by the recognition of specificmolecular patterns associated with either infection or tissue injury. The entire process of the inflammatory response ismediated by several key regulators involved in the selective expression of proinflammatory molecules. Prolongedinflammations are often associated with severe detrimental side effects on health. Alterations in inflammatory responsesdue to persistent inducers or genetic variations are on the rise over the last couple of decades, causing a variety ofinflammatory diseases and pathophysiological conditions.

Phytocytokines function as immunological modulators of plant immunity

Plant plasma membrane-resident immune receptors regulate plant immunity by recognizing microbe-associated molecular patterns(MAMPs),damage-associated molecular patterns(DAMPs),and phytocytokines.Phytocytokines are plant endogenous peptides,which are usually produced in the cytosol and released into the apoplast when plant encounters pathogen infections.Phytocytokines regulate plant immunity through activating an overlapping signaling pathway with MAMPs/DAMPs with some unique features.Here,we highlight the current understanding of phytocytokine production,perception and functions in plant immunity,and discuss how plants and pathogens manipulate phytocytokine signaling for their own benefits during the plant-pathogen warfare.