Hepatitis D virus(HDV)is a global health threat with more than 15 million humans affected.Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosi...Hepatitis D virus(HDV)is a global health threat with more than 15 million humans affected.Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosis and hepatocellular carcinoma.HDV is the only human satellite virus known.It encodes only two proteins,and requires Hepatitis B virus(HBV)envelope protein expression for productive virion release and spread of the infection.How HDV could evolve and why HBV was selected as a helper virus remains unknown.Since the discovery of Na+-taurocholate co-transporting polypeptide as the essential uptake receptor for HBV and HDV,we are beginning to understand the interactions of HDV and the immune system.While HBV is mostly regarded a stealth virus,that escapes innate immune recognition,HBV-HDV coinfection is characterized by a strong innate immune response.Cytoplasmic RNA sensor melanoma differentiation antigen 5 has been reported to recognize HDV RNA replication and activate innate immunity.Innate immunity,however,seems not to impair HDV replication while it inhibits HBV.In this review,we describe what is known up-to-date about the interplay between HBV as a helper and HDV’s immune evasion strategy and identify where additional research is required.展开更多
To the Editor: The nasopharyngeal ep让helium is frequently exposed to various harmful carcinogens. When the nasopharvngeal mucosa is damaged, local inflammation is induced.[1] Chronic inflammation of the nasopharyngea...To the Editor: The nasopharyngeal ep让helium is frequently exposed to various harmful carcinogens. When the nasopharvngeal mucosa is damaged, local inflammation is induced.[1] Chronic inflammation of the nasopharyngeal epithelium may eventually evolve into nasopharyngeal carcinoma (NPC). While the mucus secreted by the nasopharyngeal epithelium forms the body's primitive immune protection barrier as it contains a series of proteins and peptides that can sense, bind, degrade and remove various harmful substances. Lactotransferrin (LTF)[2] and bactericidal/permeability-increasing (BPI) protein family members[3] are an important component of the innate immune protection barrier.展开更多
Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participat...Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues.However,the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear.Here,we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s.ICOS costimulation enhanced the survival,proliferation,and capacity of ILC3s to produce cytokines(IL-22,IL-17A,IFN-γ,TNF,and GM-CSF).Via synergistic effects of ICOS and CD40 signaling,B cells promoted ILC3 functions,and ILC3-induced T-cellindependent B-cell IgA and IgM secretion primarily required CD40 signaling.Hence,ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.展开更多
Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the ...Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4β7 in mediating renal ILC2 adhesion and function. We found that integrin α4β7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4β7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4β7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4β7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.展开更多
Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understo...Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.展开更多
Vaccination is an effective strategy to prevent infectious or immune related diseases, which has made remarkable contribution in human history. Recently increasing atten- tions have been paid to mucosal vaccination du...Vaccination is an effective strategy to prevent infectious or immune related diseases, which has made remarkable contribution in human history. Recently increasing atten- tions have been paid to mucosal vaccination due to its multiple advantages over conventional ways. Subunit or peptide antigens are more reasonable immunogens for mucosal vaccination than live or attenuated pathogens, however adjuvants are required to augment the immune responses. Many mucosal adjuvants have been developed to prime desirable immune responses to different etiologies. Compared with pathogen derived adjuvants, innate endogenous molecules incorporated into mucosal vaccines demonstrate prominent adjuvanticity and safety. Nowadays, cytokines are broadly used as mucosal adjuvants for participation of signal transduction of immune responses, activation of innate immunity and polarization of adaptive immunity. Desired immune responses are promptly and efficaciously primed on basis of specific interactions between cytokines and corresponding receptors. In addition, some other innate molecules are also identified as potent mucosal adjuvants. This review focuses on innate endogenous mucosal adjuvants, hoping to shed light on the development of mucosal vaccines.展开更多
基金Supported by German Research Foundation,No. TRR 179
文摘Hepatitis D virus(HDV)is a global health threat with more than 15 million humans affected.Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosis and hepatocellular carcinoma.HDV is the only human satellite virus known.It encodes only two proteins,and requires Hepatitis B virus(HBV)envelope protein expression for productive virion release and spread of the infection.How HDV could evolve and why HBV was selected as a helper virus remains unknown.Since the discovery of Na+-taurocholate co-transporting polypeptide as the essential uptake receptor for HBV and HDV,we are beginning to understand the interactions of HDV and the immune system.While HBV is mostly regarded a stealth virus,that escapes innate immune recognition,HBV-HDV coinfection is characterized by a strong innate immune response.Cytoplasmic RNA sensor melanoma differentiation antigen 5 has been reported to recognize HDV RNA replication and activate innate immunity.Innate immunity,however,seems not to impair HDV replication while it inhibits HBV.In this review,we describe what is known up-to-date about the interplay between HBV as a helper and HDV’s immune evasion strategy and identify where additional research is required.
基金grants from the National Natural Science Foundation of China (Nos. 81672683, 81702907, and 81772928)the Natural Science Foundation of Hunan Province (No. 2017SK2105, 2018JJ3704, and 2018JJ3815).
文摘To the Editor: The nasopharyngeal ep让helium is frequently exposed to various harmful carcinogens. When the nasopharvngeal mucosa is damaged, local inflammation is induced.[1] Chronic inflammation of the nasopharyngeal epithelium may eventually evolve into nasopharyngeal carcinoma (NPC). While the mucus secreted by the nasopharyngeal epithelium forms the body's primitive immune protection barrier as it contains a series of proteins and peptides that can sense, bind, degrade and remove various harmful substances. Lactotransferrin (LTF)[2] and bactericidal/permeability-increasing (BPI) protein family members[3] are an important component of the innate immune protection barrier.
基金the National Key Research and Development Program(Grant 2021YFF0704800)the Science and Technology Development Program of Jilin Province(Grant 20210402009GH)+1 种基金the Science and Technology Development Program of Jilin Province(Grant YDZJ202201ZYTS098)the Norman Bethune Program of Jilin University(Grant No.2022B34).
文摘Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues.However,the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear.Here,we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s.ICOS costimulation enhanced the survival,proliferation,and capacity of ILC3s to produce cytokines(IL-22,IL-17A,IFN-γ,TNF,and GM-CSF).Via synergistic effects of ICOS and CD40 signaling,B cells promoted ILC3 functions,and ILC3-induced T-cellindependent B-cell IgA and IgM secretion primarily required CD40 signaling.Hence,ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.
基金supported by grants from the National Research Foundation of Korea(SRC2017R1A5A1014560,RS-2023-00217798,RS-2023-00211566 and NRF-2022R1A2C3007730)。
文摘Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4β7 in mediating renal ILC2 adhesion and function. We found that integrin α4β7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4β7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4β7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4β7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.
基金supported by grants from the National Center of Complementary and Alternative Medicine (NCCAM, R01AT005076)the National Institute of General Medical Sciences (NIGMS, R01GM063075)
文摘Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.
文摘Vaccination is an effective strategy to prevent infectious or immune related diseases, which has made remarkable contribution in human history. Recently increasing atten- tions have been paid to mucosal vaccination due to its multiple advantages over conventional ways. Subunit or peptide antigens are more reasonable immunogens for mucosal vaccination than live or attenuated pathogens, however adjuvants are required to augment the immune responses. Many mucosal adjuvants have been developed to prime desirable immune responses to different etiologies. Compared with pathogen derived adjuvants, innate endogenous molecules incorporated into mucosal vaccines demonstrate prominent adjuvanticity and safety. Nowadays, cytokines are broadly used as mucosal adjuvants for participation of signal transduction of immune responses, activation of innate immunity and polarization of adaptive immunity. Desired immune responses are promptly and efficaciously primed on basis of specific interactions between cytokines and corresponding receptors. In addition, some other innate molecules are also identified as potent mucosal adjuvants. This review focuses on innate endogenous mucosal adjuvants, hoping to shed light on the development of mucosal vaccines.
