• Apoptosis
• Colitis
• ER stress
• Inflammation
• Oxidative stress
• TNBS
• α-ketoglutarate

• NLRP3
• activation
• intestinal disease
• intestinal epithelial barrier
• intestinal immunity
• pharmacological targeting

• Humans
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Inflammasomes/metabolism
• Animals
• Intestinal Diseases/metabolism
• Intestinal Diseases/immunology
• Intestinal Diseases/therapy
• Intestinal Diseases/pathology
• Intestinal Diseases/drug therapy

• LYKJ[2020]29 Forestry Science and technology Programs of Jiangsu Province
• JATS[2023]355 Modern Agriculture (Flower) Industrial Technology System of Jiangsu Province
• TZDRC[2023]133 Chinese Traditional Medicine Germplasm Resources Comprehensive Utilization Engineering Research Center of Taizhou City

• MAIT cells
• T-cells
• TRM cells
• Treg cells
• gut microbiome
• reactive oxygen species
• redox
• short-chain fatty acid

• Humans
• Oxidation-Reduction
• Gastrointestinal Microbiome/immunology
• Animals
• Reactive Oxygen Species/metabolism
• Nitric Oxide/metabolism
• T-Lymphocytes/immunology
• T-Lymphocytes/metabolism

• MEFV gene
• IL-1β
• inflammatory bowel disease

• Adult
• Female
• Humans
• Male
• Middle Aged
• Young Adult
• Colitis, Ulcerative/genetics
• Collagen Type I/genetics
• Crohn Disease/genetics
• Cytoskeletal Proteins/genetics
• Genetic Predisposition to Disease
• HSP47 Heat-Shock Proteins/genetics
• Inflammasomes/genetics
• Interleukin-18/genetics
• Interleukin-1beta/genetics
• Leukocytes, Mononuclear/metabolism
• Phenotype
• Polymorphism, Single Nucleotide
• Pyrin/genetics

• 19K17430 Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research

• Gasdermin D
• Gastrointestinal cancer
• Inflammasome
• Intestinal Bowel Disease
• NLRP3
• Pyroptosis

• Humans
• Inflammasomes/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/genetics
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Pyroptosis
• Gastrointestinal Tract/metabolism
• Cytokines/metabolism
• Carcinogenesis
• Cell Transformation, Neoplastic
• Interleukin-1beta/metabolism

• RC2023 Ministero della Salute

• cancer
• inflammasome
• inflammation
• pyroptosis
• targeted treatment

• National Natural Science Foundation of China
• Project for Key Medicine Discipline Construction of Guangzhou Municipality

• Crohn’s disease
• IL-1β
• Il-10
• Il-6
• inflammatory bowel disease
• ulcerative colitis

• 503/1-002-01/503-11-001-19-00 Medical University of Lodz

Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine involved in host defense against infections and regulates the innate and acquired immune response. IL-18 is produced by both hematopoietic and non-hematopoietic cells, including monocytes, macrophages, keratinocytes and mesenchymal cell. IL-18 could potentially induce inflammatory and cytotoxic immune cell activities leading to autoimmunity. Its elevated levels have been reported in the blood of patients with some immune-related diseases, including rheumatoid arthritis, systemic lupus erythematosus, type I diabetes mellitus, atopic dermatitis, psoriasis, and inflammatory bowel disease. In the present review, we aimed to summarize the biological properties of IL-18 and its pathological role in different autoimmune diseases. We also reported some monoclonal antibodies and drugs targeting IL-18. Most of these monoclonal antibodies and drugs have only produced partial effectiveness or complete ineffectiveness in vitro, in vivo and human studies. The ineffectiveness of these drugs targeting IL-18 may be largely due to the loophole caused by the involvement of other cytokines and proteins in the signaling pathway of many inflammatory diseases besides the involvement of IL-18. Combination drug therapies, that focus on IL-18 inhibition, in addition to other cytokines, are highly recommended to be considered as an important area of research that needs to be explored.

• Antibodies, Monoclonal
• Autoimmune Diseases/immunology
• Cytokines
• Humans
• Immunity
• Inflammation/immunology
• Interleukin-18/immunology

NLRP3 inflammasome is implicated in the pathogenesis of inflammatory bowel diseases (IBD). Since guanylate-binding protein 5 (GBP5) induces the NLRP3 inflammasome activity, we aim to investigate the potential role of GBP5 in IBD pathogenesis. The expression of GBP5, NLRP3 inflammasome, and related cytokines and chemokines was examined in two cohorts of IBD patients and healthy controls, by microarray transcriptome analysis and quantitative real-time PCR. Cellular localization of GBP5 in colonic biopsies was examined by immunohistochemistry and immunofluorescence with confocal microscopy. For functional studies, GBP5 was induced by interferon γ or silenced by siRNA or CRISPR/CAS9 technique, and inflammatory activities were evaluated at mRNA and protein levels. We found that the expression of GBP5 was elevated in colonic mucosa in two geographically and culturally distinct IBD cohorts. In colonic tissues of IBD patients, GBP5 expression was mainly confined to immune cells and the levels of GBP5 expression were correlated with those of the inflammatory cytokines and chemokines. In cultured T and macrophage cells, the expression of proinflammatory cytokines and chemokines was increased when GBP5 was induced, while GBP5 deficiency leads to decreased expression of proinflammatory mediators including gasdermin D, caspase 1, cytokines, and chemokines. We conclude that GBP5 is required in the expression of many proinflammatory cytokines and chemokines in intestinal immune cells. In addition, GBP5 may upregulate inflammatory reactions through an inflammasome-mediated mechanism. Since GBP5 plays a proinflammatory role at the early steps of the inflammatory cascades of IBD pathogenesis, and is implicated in IBD patients of distinct genetic and environmental backgrounds, targeting GBP5 could be an effective strategy for the management of IBD.

• Crohn’s disease
• guanylate binding protein
• inflammasome
• pyroptosis
• ulcerative colitis

• Claudin
• Genetics
• IL23
• JAK-STAT
• MLCK
• TNF
• Tight Junction
• Toll-Like Receptor

• ACE-2
• COVID-19
• Crohn’s disease
• Inflammatory bowel disease
• SARS-CoV-2
• Ulcerative colitis

• R01 DK128143 NIDDK NIH HHS
• R03 DK123579 NIDDK NIH HHS

• Salmonella
• antimicrobial proteins
• barrier immunity
• colon
• goblet cell
• homeostasis
• inflammasome
• microbiota
• mucosal immunology
• neuroimmunology

• Animals
• Cytokines/immunology
• Enteric Nervous System/immunology
• Enteric Nervous System/metabolism
• Epithelial Cells/immunology
• Female
• Goblet Cells/immunology
• Immunity, Mucosal/immunology
• Interleukin-18/biosynthesis
• Interleukin-18/immunology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/metabolism
• Intestine, Small/immunology
• Male
• Mice
• Mice, Inbred C57BL
• Neurons/immunology
• Rats
• Rats, Sprague-Dawley
• Salmonella Infections/immunology
• Salmonella typhimurium/immunology
• Signal Transduction/immunology

• R01 GM131642 NIGMS NIH HHS
• Howard Hughes Medical Institute
• S10 OD018521 NIH HHS
• R01 HG008383 NHGRI NIH HHS
• R01 GM135928 NIGMS NIH HHS

• Cancer
• Caspase-1
• Colon
• Cytokines
• Gastric
• IFNγ, Gastrointestinal
• IL-1
• IL-12
• IL-18
• IL-18BP
• Inflammation
• Microenvironment
• NfkB
• Therapeutics

• Crohn's disease
• NLRP3 inflammasome
• gut homeostasis
• mucosal immune
• ulcerative colitis

• Animals
• Gastrointestinal Microbiome
• Humans
• Immunity, Mucosal
• Inflammasomes/physiology
• Inflammatory Bowel Diseases/etiology
• Inflammatory Bowel Diseases/immunology
• Interleukin-18/physiology
• Interleukin-1beta/physiology
• NLR Family, Pyrin Domain-Containing 3 Protein/physiology
• Pyroptosis
• Reactive Oxygen Species/metabolism

As the primary barrier between an organism and its environment, epithelial cells are well-positioned to regulate tolerance while preserving immunity against pathogens. Class II major histocompatibility complex molecules (MHC class II) are highly expressed on the surface of epithelial cells (ECs) in both the lung and intestine, although the functional consequences of this expression are not fully understood. Here, we summarize current information regarding the interactions that regulate the expression of EC MHC class II in health and disease. We then evaluate the potential role of EC as non-professional antigen presenting cells. Finally, we explore future areas of study and the potential contribution of epithelial surfaces to gut-lung crosstalk.

• MHC class II
• antigen presentation
• epithelial cells
• intestine
• respiratory

• CD161
• cytomegalovirus
• human immunodeficiency virus
• inflammatory bowel diseases
• natural killer cells
• pro-inflammatory cytokines

• Antigens, CD/immunology
• Female
• Gene Expression Regulation/immunology
• HIV Infections/immunology
• HIV Infections/pathology
• HIV-1/immunology
• Humans
• Immunity, Innate
• Integrin alpha Chains/immunology
• Killer Cells, Natural/immunology
• Killer Cells, Natural/pathology
• Male
• NK Cell Lectin-Like Receptor Subfamily B/immunology

• NIHR-RP-R3-12-026 Department of Health
• MC_UU_00008/7 Medical Research Council
• MC_UU_12010/7 Medical Research Council
• WT091663MA Wellcome Trust
• U19 AI082630 NIAID NIH HHS
• Wellcome Trust
• 109965/Z/15/Z Wellcome Trust

The expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.

We employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid). We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.

In the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF) by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40%) and gp96-II peptide (35%). Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%), lipopolysaccharide-induced TNF (48%), IL-6 (81%) and in Staphylococcus epidermidis-induced TNF (67%) and IL-6 (81%), as well as IL-12/IL-18-induced IFNγ (75%). gp96-II peptide reduced IL–1β, IL-6, TNF and GM-CSF in human peripheral blood mononuclear cells to a similar degree without affecting cell viability, whereas RANTES, IL-25 and MIF were twofold to threefold increased.

gp96-II peptide protects against murine intestinal inflammation by regulating inflammation in vivo and in vitro, pointing to its promise as a novel treatment for inflammatory bowel disease.

• Gp96
• anti-inflammatory agent
• biologics
• cytokines and inflammation
• immunemodulatory
• inflammatory bowel disease
• intestinal inflammation
• therapeutics

Apoptosis inhibitor of macrophages (AIM) was initially identified as an apoptosis inhibitor that supports the survival of macrophages against various apoptosis-inducing stimuli, and AIM produced by macrophages may contribute to the pathogenesis of inflammatory bowel diseases (IBDs). However, there have been no reports on the kinetics of AIM in IBD and the impact of AIM on the pathogenesis of IBD. In this study, we aimed to investigate the diagnostic utility of levels of AIM and their correlation with the activity of Crohn’s disease (CD) and IBD.

We used an enzyme-linked immunosorbent assay (ELISA) to examine AIM serum levels in 16 healthy subjects and 90 patients with inflammatory bowel diseases, namely 39 with CD and 51 with ulcerative colitis (UC), as well as 17 patients with Behcet’s disease (BD) as intestinal disease controls. We compared serum AIM levels among groups and examined whether there were correlations between serum AIM levels and disease activity and type. We also performed immunohistochemical staining of AIM in intestinal tissues of patients with CD.

Serum AIM levels were significantly higher in patients with CD than in patients with UC, BD, and controls (3.27 ± 2.14, 1.88 ± 1.43, 2.34 ± 1.37, and 2.13 ± 0.64 μg/ml, respectively; P < 0.01). There was no difference in serum AIM levels before and after treatment in patients with CD. However, in these patients the diagnostic rate using AIM was better than that based on anti-Saccharomyces cerevisiae antibodies. AIM was expressed in macrophages that were positive for CD14, CD16, or both in the intestinal tissues of patients with CD.

AIM is a novel biomarker of CD that can distinguish CD from UC or BD. It is suggested that AIM may contribute to intestinal inflammation by inhibiting the apoptosis of macrophages.

• Apoptosis inhibitor of macrophages
• Crohn’s disease
• Inflammatory bowel diseases
• Macrophages

• Autoimmune disease
• Intestine
• Macrophages
• Monocytes

• Animals
• Autoimmune Diseases/immunology
• Humans
• Immunity, Mucosal
• Intestinal Mucosa/immunology
• Macrophages/immunology
• Monocytes/immunology
• Toll-Like Receptors/immunology

• R01 AI091526 NIAID NIH HHS
• I01 BX000470 BLRD VA
• I01 CX001211 CSRD VA
• UL1 RR029882 NCRR NIH HHS
• R01 AI077283 NIAID NIH HHS
• P60 AR062755 NIAMS NIH HHS

• CD39
• OX40
• T follicular regulatory
• Tfh
• Th17
• colorectal cancer
• helios
• tregs

Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT).

Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman’s correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn’s post-test and the Mann–Whitney U tests.

None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-α and IL-1β with CD68⁺ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14⁺ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14⁺ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS.

Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.

• Cytokines
• IL-15
• Inflammation
• MAIT-cells
• T cells

Chronic periodontitis is characterized by perturbation of the epithelial attachment to the tooth with subsequent migration of the lining epithelium and formation of a cleft or pocket. This non-keratinized lining epithelium provides initial responses to bacterial products by signalling through receptors of innate immunity to activate inflammasome pathways. These comprise an intracellular network of regulatory and effector molecules leading to synthesis and activation of pro-inflammatory cytokines. Conversely, CD24 is characteristically strongly expressed by the pocket epithelium and is reported to function as an important negative regulator for danger signals, protecting tissues from excessive leukocyte activity. The objective of the study was to determine the impact of ligation of CD24 on expression of inflammasome components. An epithelial mimic of pocket epithelium was used to evaluate activation of the NLRP3 inflammasome pathway. Surprisingly, antibody ligation of CD24 enhanced expression of NLRP3 together with co-activators ASC and caspase-1 resulting in burst release of activated interleukin (IL)-18. Potent product inhibition was detected with IL-18 suppressing expression of NLRP3, ASC, and caspase-1. Scant distribution of these products within pocket epithelium compared with healthy gingival attachment provided indication of potential cycling of NLRP3 inflammasome expression. As subjects with mild chronic periodontitis have increased titres of serum antibodies auto-reactive with CD24 compared with those of subjects with severe periodontitis, a molecular mechanism for regulated expression of the NLRP3 inflammasome mediated by c-Src kinase activity, is proposed. This pathway could be regionally disrupted by products of pathogenic bacteria with profound downregulation in the dysbiosis associated with severe disease.

• CD24
• NLRP3
• inflammasome
• periodontitis

Recent studies have suggested that IL-18 −607C/A and −137G/C polymorphisms may be associated with the risk of allergic disease; however, individually published results are inconclusive. Therefore, we performed a meta-analysis to clarify whether IL-18 −607C/A and −137G/C polymorphisms were associated with the risk of allergic disease. A total of 21 studies including 5,331 cases and 9,658 controls were involved in this meta-analysis. In the overall analysis and the subgroup analysis according to ethnicity, we did not find significant association between IL-18 −607C/A or −137G/C polymorphism and the risk of allergic disease (all P > 0.05). However, in a stratified analysis by type of allergic disease, our results indicated that IL-18 −607C/A polymorphism was associated with a significantly decreased risk of allergic asthma in heterozygous comparison and IL-18 −137G/C was associated with a significantly decreased risk of allergic dermatitis in recessive model and homozygous comparison. In the stratified analysis by source of control, IL-18−607C/A showed significantly reduced risk in population-based subgroup, and for IL-18 −137G/C only significantly decreased risk was found in the hospital-based subgroup. Our meta-analysis suggests that IL-18 −607C/A and −137G/C polymorphisms may be protective factors for the risk of allergic asthma and allergic dermatitis, respectively.

• cytokines
• interleukins
• inflammatory bowel disease

In addition to their well-established role(s) in the pathogenesis of gastrointestinal (GI)-related inflammatory disorders, including inflammatory bowel disease (IBD) and inflammation-associated colorectal cancer (CRC), emerging evidence confirms the critical involvement of the interleukin-1 (IL-1) cytokine family and their ligands in the maintenance of normal gut homeostasis. In fact, the paradigm that IBD occurs in two distinct phases is substantiated by the observation that classic IL-1 family members, such as IL-1, the IL-1 receptor antagonist (IL-1Ra), and IL-18, possess dichotomous functions depending on the phase of disease, as well as on their role in initiating vs. sustaining chronic gut inflammation. Another recently characterized IL-1 family member, IL-33, also possesses dual functions in the gut. IL-33 is upregulated in IBD and potently induces Th2 immune responses, while also amplifying Th1-mediated inflammation. Neutralization studies in acute colitis models, however, have yielded controversial results and recent reports suggest a protective role of IL-33 in epithelial regeneration and mucosal wound healing. Finally, although little is currently known regarding the potential contribution of IL-36 family members in GI inflammation/homeostasis, another IL-1 family member, IL-37, is emerging as a potent anti-inflammatory cytokine with the ability to down-regulate colitis. This new body of information has important translational implications for both the prevention and treatment of patients suffering from IBD and inflammation-associated CRC.

• IL-1 family of cytokines
• Toll/IL-1 receptor family
• colitis
• inflammation-associated colon cancer
• inflammatory bowel disease
• intestinal fibrosis
• intestinal homeostasis
• mucosal wound healing

Bile acids (BAs) play important roles not only in lipid metabolism, but also in signal transduction. TGR5, a transmembrane receptor of BAs, is an immunomodulative factor, but its detailed mechanism remains unclear. Here, we aimed to delineate how BAs operate in immunological responses via the TGR5 pathway in human mononuclear cell lineages. We examined TGR5 expression in human peripheral blood monocytes, several types of in vitro differentiated macrophages (Mϕs) and dendritic cells. Mϕs differentiated with macrophage colony-stimulating factor and interferon-γ (Mγ-Mϕs), which are similar to the human intestinal lamina propria CD14⁺ Mϕs that contribute to Crohn's disease (CD) pathogenesis by production of pro-inflammatory cytokines, highly expressed TGR5 compared with any other type of differentiated Mϕ and dendritic cells. We also showed that a TGR5 agonist and two types of BAs, deoxycholic acid and lithocholic acid, could inhibit tumour necrosis factor-α production in Mγ-Mϕs stimulated by commensal bacterial antigen or lipopolysaccharide. This inhibitory effect was mediated by the TGR5–cAMP pathway to induce phosphorylation of c-Fos that regulated nuclear factor-κB p65 activation. Next, we analysed TGR5 levels in lamina propria mononuclear cells (LPMCs) obtained from the intestinal mucosa of patients with CD. Compared with non-inflammatory bowel disease, inflamed CD LPMCs contained more TGR5 transcripts. Among LPMCs, isolated CD14⁺ intestinal Mϕs from patients with CD expressed TGR5. In isolated intestinal CD14⁺ Mϕs, a TGR5 agonist could inhibit tumour necrosis factor-α production. These results indicate that TGR5 signalling may have the potential to modulate immune responses in inflammatory bowel disease.

• IL-18
• IL-18 binding protein
• Toxoplasma gondii
• ileitis
• immunopathology

• Adaptive Immunity
• Animals
• Autoimmune Diseases/immunology
• Cardiovascular Diseases/immunology
• Humans
• Immunity, Innate
• Inflammation/immunology
• Interleukin-1/immunology
• Interleukin-1/metabolism
• T-Lymphocytes/immunology
• T-Lymphocytes/metabolism

• Adenocarcinoma/blood
• Adenocarcinoma/mortality
• Adenocarcinoma/secondary
• Aged
• Bone Neoplasms/blood
• Bone Neoplasms/mortality
• Bone Neoplasms/secondary
• Bone and Bones/metabolism
• Carcinoma, Non-Small-Cell Lung/blood
• Carcinoma, Non-Small-Cell Lung/mortality
• Carcinoma, Non-Small-Cell Lung/secondary
• Female
• Humans
• Immunohistochemistry
• Interferon-gamma/blood
• Interleukin-18/biosynthesis
• Interleukin-18/blood
• Japan/epidemiology
• Lung/metabolism
• Lung Neoplasms/blood
• Lung Neoplasms/mortality
• Male
• Middle Aged
• Survival Analysis
• Thioredoxins/blood

Inflammatory bowel disease (IBD) is closely associated with the abnormal immune response of intestinal immune system to enterobacteria and dietary antigens. Large amounts of mononuclear lymphocyte infiltrates and high expression levels of proinflammatory cytokines and costimulatory molecules are present in inflamed mucosa. NK cells, involved in innate and acquired immune response, have cytolitic activities through secretion of lytic proteins, and produce proinflammatory mediators. Increased infiltration of NK cells present in inflamed mucosa of IBD expresses high levels of activated molecules and proinflammatory cytokines, and plays a role in intestinal mucosal damage.

• Inflammatory bowel disease
• NK cell
• Immune response