In 2023,numerous theoretical advancements and technological breakthroughs have been achieved in the field of immunology research.In this article,we summarized representative research achievements in the field of immunology both domestically and internationally in 2023,and discussed the challenges and opportunities for future research.

The type Ⅱ inflammatory response is primarily mediated by type 2 immune cells and cytokines,such as helper 2 cells(Th2)and group 2 innate lymphoid cells(ILC2),along with IL-4,IL-5 and IL-13.This response plays crucial roles in humoral immunity,parasite defense,toxin neutralization,tissue damage repair and regeneration.However,type-Ⅱ immune response can also contribute to the development of diseases.Currently,type Ⅱ inflammation is recognized to have physiological and pathological impli-cations in the skin,respiratory tract,digestive tract and adipose tissues.Moreover,it serves as a major cause of allergic diseases.Due to its unique immune microenvironment,the respiratory tract exhibits a high prevalence of type Ⅱ inflammation encompassing chronic sinusitis,allergic rhinitis,allergic asthma,allergic bronchopulmonary aspergillosis,and chronic obstructive pulmonary disease with eosinophilia among others.This review will focus on the research progress concerning Th2 and ILC2 cells in allergic pulmonary inflam-mation as well as targeted therapy for allergic diseases.

NK cells are important components of innate immune system and play a key role in immune responses.Activation of NK cells mainly depends on dynamic balance between activatory and inhibitory receptors expressed on surface.However,in many chronic diseases,balance between these receptors of NK cells is disorder,resulting in reduced cytolysis activity and cytokine produc-tion,which is in a state of immune inactivation.In recent years,many studies have shown that intracellular metabolism is crucial for immune cells such as NK cells,and changes of metabolism will regulate functions of immune cells by affecting cell development,pro-liferation and activity.In view of powerful anti-tumor and anti-viral effects of NK cells and their important clinical application value,it is important to study their metabolic characteristics and mechanisms.This review mainly introduces metabolic patterns of NK cell,related regulatory pathways,regulatory effects of metabolism on NK cell development,memory and functions,and metabolism-based NK cell therapy,also expounds important role of metabolism on NK cell biosynthesis,stability and effector function in vivo,as well as metabolism-related factors involved in NK cell inactivation in different chronic diseases,providing a solid research basis for clinical application of NK cell therapy.

The immune system is the defender of human health,whose dysregulation is the source of various diseases.Re-duced immune defense and immune surveillance capabilities lead to difficulties in removing pathogens and malignant cells,thus increasing morbidity and mortality risk.Stress is a major factor in the decline of the immune system.In past studies,it has been demon-strated both in animal and humans that stress increases the levels of neuroendocrine hormones in the body,particularly glucocorticoids and catecholamines.Through the action of these stress hormones,stress has a number of detrimental effects on immune function,and this review combs through the progress of research on the regulation of immune cells by glucocorticoids.

Immunologic skin diseases encompass a spectrum of immune system-mediated autoimmune or inflammatory skin conditions,such as lupus erythematosus,psoriasis,atopic dermatitis,and vitiligo.Immunologic skin diseases are characterized by an unclear pathogenesis,complex disease processes,diverse clinical manifestations,and treatment difficulties,thereby presenting sig-nificant diagnostic and therapeutic challenges.Notably,Chinese researchers have achieved numerous innovative research findings on immunologic skin diseases in recent years.Over the past decade,Chinese scholars have contributed 11 919 SCI papers to the field of immune dermatosis,with more than 10 being published in the world's leading medical journals.These publications include one in Sci-ence,one in Nature,two in Cell,three in The New England Journal of Medicine,two in The Lancet,and one in Nature Medicine,as well as four in Immunity.Here,we aim to present a comprehensive summary of Chinese research progress pertaining to the pathogene-sis,diagnosis and treatment of immunologic skin diseases.

Objective:To construct a mouse asthma model induced by mugwort pollen and to explore endotyping,providing methods for subsequent precision treatment.Methods:BALB/c mice were intraperitoneally injected with mugwort pollen extract(MPE)to sensitize,following MPE intranasal challenge to construct MPE allergic asthma murine model.Mice were randomly divided into PBS sensitization and PBS challenge(P-P),MPE sensitization and PBS challenge(M-P),MPE sensitization and MPE challenge model(M-M)groups.24 h after final challenge,mice were performed to examine airway responsiveness;bronchoalveolar lavage fluid(BALF)was harvested for cell counting and statistical classification of inflammatory cells through flow cytometry analysis.Pulmonary slides were collected for pathological examination,including HE,PAS,Masson and α-SMA immunohistochemical staining.ELISA was used to detect levels of IFN-γ,IL-4,IL-5,IL-13,IL-17A in lung tissue and serum,as well as serum total IgE and MPE-specific IgE,IgG1,IgG2a levels.Results:Pathological examination showed higher airway reactivity,more inflammatory cells infiltration around airway,obvious goblet metaplasia,thickening of airway smooth muscles and dramatical fibrin deposition around airway in model group.Total cell numbers of BALF were increased from<1×105 cells/ml in P-P group to>5×105 cells/ml in model group,in which eosinophils were predominant cellular type,levels of IL-4,IL-13,IL-17A in lung and IL-5,IL-13 levels in serum were significantly increased,as well as significant increasing levels of total IgE and MPE-specific IgE,IgG1,IgG2a.Conclusion:MPE-sensitized and challenged mice induces typical eosinophilic asthma featured with elevated eosinophils,as well as secretion of inflammatory factors of type 2 and type 17,IgE,IgG1 and IgG2a subtypes soars to high levels.

Objective:To analyze identification of copper death gene related subtypes,construction of prognosis model and influence of immune infiltration in osteosarcoma(OS)on basis of copper death gene.Methods:Survival and prognosis of OS associated copper death gene were analyzed combining by TARGET and GEO database.OS was divided into different subtypes of copper death by consistent clustering method.SSGSEA was used to analyze difference of immune cells in classification of copper death.Setting P value= 0.05 and q value=0.05,GO and KEGG enrichment analysis were performed on differential genes of copper death typing.Prognosis model was constructed according to results of Lasso regression analysis and cross validation,risk assessment analysis and ROC curve were used to evaluate accuracy of model prediction.Combined with clinical characteristics,nomograms were constructed to predict survival time of patients,and risk differences were analyzed.Immune cell infiltration and tumor microenvironment analysis were performed on OS samples."pRRophetic"package in R software was used to analyze drug sensitivity of OS samples.Results:FDX1,GLS,DLAT and PDHB as high-risk genes for OS prognosis were identified.According to copper death classification of OS samples,OS could be divided into two types:CRGclusterA and CRGclusterB.CRGclusterA was associated with Th2 cells,and CRGclusterB was associated with Th1 cells.Most OS copper death genes were highly expressed in CRGclusterA.Immune cell infiltration analysis results showed that γδ T cells,resting mast cells and resting dendritic cells were positively correlated with risk score,while CD8 T cells were negatively correlated with risk score.Drug sensitivity analysis showed that OS showed higher sensitivity to Elesclomol and GW.441756.Conclusion:Two subtypes of CRGclusterA and CRGclusterB are identified in this study.Four high-risk prognostic genes FDX1,GLS,DLAT and PDHB are identified,providing new insights into prognostic evaluation and immunotherapy target candidates for OS.

Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.

Objective:To demonstrate the polymorphism of α chain of bovine major histocompatibility complex(BoLA)classⅠmolecule and domain binding constant chain(Ii).Methods:Total 75 BoLA Iα genes were obtained from three Huaibei cattle and analyzed by molecular biology software;the genes of typical BoLA Iα domains and Ii were cloned,and then inserted into prokaryotic expression plasmid.After induced protein expression;the domains of BoLA Ⅰα chain binding to Ii were detected by pull-down meth-od and Western blot.The recombinant eukaryotic expression plasmids were constructed and the co-localization of BoLA Iα segments with Ii was observed by laser confocal microscopy.Results:Firstly,it was found that there were at least 5 kinds of BoLA Iα in the cloned gene sequence,which were highly polymorphic and they were mainly distributed in the antigen peptide binding region(PBR)of BoLA Ⅰ(α1α2)and cytoplasmic region.Secondly,the prokaryotic recombinant plasmids containing BoLA Ⅰα1α2α3,BoLA Ⅰα1α2 or BoLA Ⅰα 3 were constructed,then they were respectively induced to express and purified,in which,the BoLA Ⅰα1α2α3 and BoLA Ⅰα1α2 had the activity of binding to Ii.Finally,in 293T cells BoLA Ⅰα1α 2α3 or BoLA Ⅰα1α2 was found that could co-localize with Ii,while a single BoLA Ⅰα3 could not.Conclusion:BoLA Ⅰα gene is highly polymorphic.BoLA Ⅰα1α2 is a func-tional fragment that binds to Ii and co-locates intracellular.

Objective:To determine whether human papillomavirus(HPV L1)C-terminal conserved sequence antibodies with cross-reactive major capsid proteins of different types of HPV L1 have the ability to degrade HPV6 infection.Methods:Condyloma specimens were collected,HPV6 infection cases were identified from the collected samples,and virus was extracted.Polypeptide anti-sera were diluted in different proportions,and then co-cultured and neutralized with the resulting virus,then removed to contact mono-layer-cultured human immortalized keratinocytes and tested by HPV6 disease using PCR.Content of HPV6 DNA in human immortalized keratinocytes was exposed,and the presence of HPV6 L1 protein in this cells was tested by ELISA.Results:Human immortalized ke-ratinocytes infected with HPV6 virus neutralization at different dilution concentrations,the PCR products of their DNA extracts were electrophoresis and showed positive bands of HPV6 specificity zone at 280 bp of the gel,and the intensity of positive bands gradually decreased with increasing antiserum concentration.Protein extracted from human immortalized keratinocytes exposed to anti-serum neutralizing virus was tested by ELISA,and the amount of HPV L1 protein showed the same gradient trend as the above PCR test results,and the difference were statistically significant.Conclusion:It is preliminarily proved that HPV6 L1 conserved sequence polypeptide antisera can partially degrade the infection ability of the virus,and it has the value of studying more HPV neutralization types.