Lymphocytes In Intestinal Mucosa Research Articles

Dual regulation effect and mechanism of human myeloid-derived suppressor cells on anticolorectal cancer cells activity of Vγ9Vδ2 T cells.

Myeloid-derived suppressor cells (MDSC) are a group of immature inhibitory cells of bone marrow origin. Human γδ T cells (mainly Vγ9Vδ2 T cells) have emerged as dominant candidates for cancer immunotherapy because of their unique recognition pattern and broad killing activity against tumor cells. Intestinal mucosal intraepithelial lymphocytes are almost exclusively γδ T cells, so it plays an important role in inhibiting the development of colorectal cancer. In this study, we investigated the effects and molecular mechanism of human MDSC on anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our results suggested that MDSC can reduce the NKG2D expression of Vγ9Vδ2 T cells through direct cell-cell contact, which is associated with membrane-type transforming growth factor-β. In contrast, MDSC can increase Vγ9Vδ2 T cells activation and production of IFN-γ, perforin, Granzyme B through direct cell-cell contact. This may be related to the upregulation of T-bet in Vγ9Vδ2 T cells by MDSC. However, MDSC had a dominant negative regulatory effect on the anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our study provides a theoretical basis for the immune regulatory function of human MDSC on γδ T cells. This will be conducive to the clinical development of a new antitumor therapy strategy.

Lactobacillus fermentum Stimulates Intestinal Secretion of Immunoglobulin A in an Individual-Specific Manner.

Immunoglobulin A (IgA), as the most secreted immunoglobulin in the intestine, plays an irreplaceable role in mucosal immunity regulation. Previous studies have indicated that Lactobacillus showed strain specificity in stimulating the secretion of IgA through intestinal mucosal lymphocytes. The reason for this phenomenon is not clear. The current studies have been aimed at exploring the effect of a strain on the secretion of IgA in the host’s intestine, but the mechanism behind it has not been seriously studied. Based on this, we selected five strains of Lactobacillus fermentum isolated from different individuals to determine whether there are intraspecific differences in stimulating the secretion of IgA from the intestinal mucosa. It was found that IgA concentrations in different intestinal segments and faeces induced by L. fermentum were different. 12-1 and X6L1 strains increased the secretion of IgA by the intestine significantly. In addition, different strains of L. fermentum were also proven to have different effects on the host gut microbiota but no significant effects on IgA-coated microbiota. Besides, it was speculated that different strains of L. fermentum may act on different pathways to stimulate IgA in a non-inflammatory manner. By explaining the differences of IgA secretion in the host’s intestine tract stimulated by different strains of L. fermentum, it is expected to provide a theoretical basis for the stimulation of intestinal secretion of IgA by Lactobacillus and a new direction for exploring the relationship between Lactobacillus and human immunity.

WC1+ and WC1neg γδ T lymphocytes in intestinal mucosa of healthy and Mycobacterium avium subspecies paratuberculosis-infected calves

Mucosal surfaces such as the gastrointestinal tract, and skin are the front line of host defence and immunity against many pathogens. Gamma delta (γδ) T lymphocytes preferentially localize to the mucosal surfaces in several species including cattle, and are thought to play crucial roles in immunosurveillance and host defence, particularly against mycobacteria. Many γδ T cells are present in young calves, which is the period when calves are thought to be initially exposed to Mycobacterium avium subspecies paratuberculosis (Map). The role of mucosal γδ T cells in cattle, especially during host-pathogen interactions during early pre-clinical phases of infectious disease remains unclear. The purposes of this study were to investigate and characterize WC1+ and WC1neg γδ T cell subsets in various segments of the gastrointestinal (GI) tract of young calves, and then to examine γδ T cell subsets in the distal small intestine of calves after experimental intestinal Map infection by direct Peyer’s patch inoculation. We show that in healthy calves, the relative proportion of γδ T cells is constant throughout the GI mucosa, though the ileum has significantly more γδ T cells. In the distal intestine, γδ T cells are mainly WC1neg and primarily located within the lamina propria of the jejunum and ileum. In Map-infected intestine, there are higher numbers of γδ T cells in the lamina propria and a greater proportion of WC1+ cells within the epithelial layer compared to control calves. While WC1neg γδ T cells preferentially localize to the distal small intestine of healthy calves, WC1+ γδ T cells are increased in the intestinal mucosa during Map infection, which is suggestive of effector cell function. Further, spectral microscopy and flow cytometry in tandem will lead to improved understanding of the functions of these cells during health and disease.

Extracellular overproduction of E7 oncoprotein of Iranian human papillomavirus type 16 by genetically engineered Lactococcus lactis

BackgroundWe aimed at constructing Lactococcus lactis strains expressing HPV-16 recombinant E7 (rE7) oncoprotein and examining its overproduction ability followed by optimizing batch and fed-batch fermentations. Thereafter, in order to assess the immunogenicity of recombinant L. lactis cells, C57BL/6 mice were immunized by oral gavage.ResultsThe results suggested that recombinant strains harboring optiE7 and E7 genes produced a maximum of 4.84 and 1.91 μg/mL of rE7 in static flask experiments, while the corresponding strains gave a maximum yield of 35.49 and 14.24 μg/mL in batch experiments, respectively. Fed-batch study indicated that the concentration of rE7 protein significantly increased after feeding yeast extract plus GM17 medium. The rE7 production of the best performing strains was 2.09- and 1.48-fold higher than that of the strains during the batch fermentation. Furthermore, biomass levels were 1.98- and 1.92-fold higher than those in batch cultivation. Oral immunization of C57BL/6 mice with recombinant L. lactis produced significant specific IgG and IgA antibody responses in serum and vaginal fluids, respectively. Our outcomes suggest that vaccination with L. lactis expressing rE7 can generate significant protective effects against E7-expressing cell line. Also, our study provides evidence that the presence of large amounts of E7-specific CD4+ T helper and CD8+ T cell precursors was stimulated. Significantly higher frequencies of HPV-16 E7 specific IL-2- and IFN-γ-secreting T cells were detected in antigen-stimulated splenocytes and intestinal mucosal lymphocytes, when compared to the control groups.ConclusionsWe conclude that optimization of culture conditions along with recombinant protein expression can highly stimulate both specific humoral and cell-mediated immune responses in mice after oral immunization. These promising results represent a step towards fast-tracking a vaccine against HPV-16-associated cervical cancer.

Protection against human papillomavirus type 16-induced tumors in C57BL/6 mice by mucosal vaccination with Lactococcus lactis NZ9000 expressing E6 oncoprotein

Recombinant strains of Lactococcus lactis NZ9000 that express native and codon-optimized E6 protein (fused to the SPusp45 secretion signal) were successfully constructed by using the nisin-controlled gene expression (NICE) system. Expression of the recombinant strains was evaluated by Western blot analysis. Female mice of strain C57BL/6 were immunized orally with recombinant lactococci expressing inducible E6 oncoprotein and the antigen-specific antibody production (IgA and IgG) and cytokines were measured by ELISA and ELISPOT assay, respectively. Our outcomes indicate that the HPV-16 E6 specific IL-2- and IFN-γ-secreting lymphocytes in the antigen-stimulated intestinal mucosal lymphocytes, splenocytes and vaginal lymphocytes were significantly higher than the control groups. We showed that L. lactis having codon-optimized E6 oncogene had better inhibitory effect on tumor growth, better treatment effects on progression of tumor size, and better survival rate in comparison with L. lactis having native E6 oncogene, (P < 0.0001).In conclusion, the rE6 protein displayed by L. lactis can induce humoral and cellular immunity. Taken together, these preclinical results represent a promising step towards the development of recombinant L. lactis as a live oral vector vaccine to treat the HPV-16 associated with cervical cancer.

Oral immunization with recombinant Lactococcus lactis NZ9000 expressing human papillomavirus type 16 E7 antigen and evaluation of its immune effects in female C57BL/6 mice.

The ORFs of both native and codon-optimized E7 genes were successfully fused to SPusp45 signal peptide and expressed by a nisin-controlled gene expression system in the NZ9000 strains of Lactococcus lactis. Recombinant strains were confirmed by Western blot analysis. To measure immune responses against the E7 antigen, specific-pathogen-free C57BL/6 mice were inoculated with L lactis harboring pNZ8123-rE7 by oral gavage. Then, specific antibodies and cytokines were measured by enzyme-linked immunosorbent assay and enzyme-linked immunospot assay, respectively. Oral administration of L lactis strains expressing rE7 elicited the highest levels of E7-specific antibody and greatest numbers of E7-specific CD4+ T helper and CD8+ T cell precursors. Our outcomes indicated that the HPV-16 E7 specific IL-2- and IFN-γ-secreting T cells in antigen-stimulated splenocytes and intestinal mucosal lymphocytes were significantly higher than the control groups. Our data also demonstrated that mice vaccinated with recombinant L lactis were able to generate potent protective effects against challenge with the E7-expressing tumor cell line (TC-1). Moreover, L lactis containing pNZ8123-HPV16-optiE7 showed strong therapeutic antitumor effects against established tumors in vivo. These findings demonstrate that recombinant L lactis induce both humoral and cellular immune responses in mice and are therefore recommended for therapeutic treatments in humans after oral administration.

Lymphocytic duodenitis or microscopic enteritis and gluten-related conditions: what needs to be explored?

Microscopic enteritis (ME) is characterized by abnormal infiltration of intraepithelial lymphocytes in intestinal mucosa. It was described as duodenal lymphocytosis or lymphocytic duodenitis until the dedicated Consensus Conference of 2015. ME represents a common feature of several gluten-mediated and non-gluten related diseases; therefore, it is an umbrella term embracing several conditions. The most frequent causes of ME are gluten-related disorders (celiac disease, non-celiac gluten sensitivity, wheat allergy), Helicobacter pylori infection and drug-related damages. Less frequently, ME may be secondary to inflammatory bowel disease, some autoimmune conditions, immunoglobulin deficiencies, blood malignancies, infections and irritable bowel syndrome. Therefore, the differential diagnosis of ME may be challenging. The diagnosis of ME needs to be driven by predominant symptoms and patient history. However, it is often difficult to achieve an immediate identification of the underlying condition, and a broad variety of diagnostic tests may be required. Ultimately, long-term surveillance is needed for a final diagnosis in many cases, since a hidden or quiescent condition may be disclosed after a period of latency. In any case, strict collaboration between the clinician and the pathologist is pivotal. The treatment of ME should be personalized, depending on the underlying disease. For gluten-related conditions (celiac disease, gluten sensitivity, wheat allergy, dermatitis herpetiformis), a gluten-free diet may be proposed. For other conditions, a targeted etiologic treatment is necessary. In conclusion, ME represents a novel entity that is attracting increasing interest. The growing epidemiologic trend confirms that it will become a common condition in clinical practice.

Development of new therapies targeting human papillomavirus molecules

High-risk HPV E6 and E7 oncogenes are an ideal targeting gene for treatment of cervical cancer. In this paper, we introduce researches on cancer-immunotherapy targeting HPV E7 through mucosal immunity and E6/E7-targeting siRNA therapy using PEGylated polymeric micelles. Therapeutic HPV vaccine has also attracted attention as a cancer immunotherapy agent. We have found homing of Integrin β7-positive intestinal mucosal lymphocyte on the cervical mucosa. In this study, we generated a novel therapeutic vaccine; an HPV E7-expressing Lactobacillus casei (LacE7) to induce anti-HPV cellular immunity directly to intestinal mucosa. Cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were counted E7 specific INFγ-producing cells (E7 cell-mediated immune responses: E7-CMI) by ELISPOT assay. We confirmed induction of anti-E7 IFNγ-producing cells in the cervix lymphocytes obtained from these patients. E6/E7 siRNA therapy requires a delivery system for its systemic intravenous administration. We here demonstrated that intravenous injection of HPV16 or 18 E6/E7 siRNA polymeric micelles suppressed excellently an increase in size of subcutaneous tumor formed by SiHa or HeLa cell, respectively. Our drug-delivery technology using polymeric micelles enabled the successful systemic administration of siRNA to exhibit anti-tumor effect.

Activation of PI3K/Akt/mTOR signaling pathway triggered by PTEN downregulation in the pathogenesis of Crohn's disease

We aimed to investigate the role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway and its negative feedback factor, phosphatase and tensin homolog (PTEN), in the pathogenesis of Crohn's disease (CD). Peripheral blood was collected from patients with CD and healthy controls while colon tissue samples were collected from CD patients and those complaining of constipation but with normal endoscopic results. CD4⁺ T-cells were isolated from peripheral blood. The expression of PI3K/Akt/mTOR pathway components and PTEN was evaluated in the peripheral CD4⁺ T-cells using polymerase chain reaction and Western blot, and in intestinal mucosal lymphocytes using immunohistochemistry. mRNA expressions of PI3K, Akt, mTOR, 4E-binding protein 1 (4E-BP1) and phosphate-ribosomal protein S6 kinase (p70S6K) in peripheral CD4⁺ T-cells were upregulated in CD patients compared with healthy controls . However, the differences were not significant (P > 0.05). Western blot showed that the ratios of phospho-Akt: Akt, phosphorylated-4E-BP1: 4E-BP1 and phospho-p70S6K: p70S6K in peripheral CD4⁺ T-cells were higher in CD patients (P < 0.05). The composite staining score of phospho-Akt and phospho-mTOR in intestinal mucosal lymphocytes also increased in patients with CD compared with those with constipation. Both PTEN mRNA and protein expressions in either peripheral CD4⁺ T-cells or mucosal lymphocytes were lower in patients with CD than in the healthy controls and those with constipation. The PI3K/Akt/mTOR signaling pathway was activated in CD. The activation of the PI3K/Akt/mTOR pathway caused by PTEN downregulation may be involved in the pathogenesis of CD.

Reciprocal Interaction Between Intestinal Microbiota and Mucosal Lymphocyte in Cynomolgus Monkeys After Alemtuzumab Treatment

It has been known that the gut microbiota plays a central role in shaping normal mucosal immunity, however, little information is available whether the variability of mucosal lymphocytes impacts the commensal flora. Here, we applied a cynomolgus monkey model to characterize the structure and composition of the gut microbiota in response to lymphocyte depletion and to determine their potential association. Molecular profiling of 16S rDNA showed that the intestinal microbiota composition was perturbed after the depletion of mucosal lymphocytes and were recovered following the repopulation. Some specific bacteria from the orders Lactobacillales, Enterobacteriales and Clostridiales, and the genus Prevotella and Faecalibacterium, were primarily responsible for the variations of the gut microbiota after lymphocyte depletion. Interestingly, the species richness of the ileal mucosal microbiota was associated the proportions of TCRαβ+ or TCRγδ+ T cells (p<0.01). We demonstrate for the first time the feature of intestinal microbiota composition after lymphocyte depletion and provide novel evidence that the perturbation of gut microbiota is associated with lymphocyte depletion. It may contribute to understand the relationship between gut commensal microbiota and mucosal immune system. Study results provide insight into biological activity of alemtuzumab in intestinal barrier in organ transplantation.

Dietary oils modulate T-cell differentiation and IL-2 bioactivity of intestinal mucosal lymphocytes in chickens

The study was conducted to investigate the effects of dietary oils on the differentiation of intestinal lymphocytes and cytokines generation in chickens. One hundred and eighty chickens were assigned to three groups in one factorial design. Factor was dietary fat types (4.5% poultry oil, 4.5% corn oil or 4.5% fish oil). The proportion of CD3+CD4+ lymphocytes of intestinal mucosal lymphocytes (IMLs) in chickens fed fish-oil diets on 21 d and 42 d of age was significantly higher than those in chickens fed corn-oil and poultry-oil diets (P <0.01). And the proportion of intestinal CD3+CD8+ lymphocytes of chickens fed fish-oil diets was significantly lower than those of chickens fed corn-oil and poultry-oil diets (P <0.01) on 21 d and 42 d of age. Fish-oil consumption enhanced IL-2 secretion of IMLs stimulated with concanavalin A (ConA) (P <0.01), compared with poultry oil; but corn-oil consumption decreased IL-2 secretion than poultry-oil diets (P <0.01). Fish oil decreased the mRNA abundance of calcitonin gene-related peptide (cGRP) in intestinal mucosa of chickens on 21 d and 42 d of age compared to poultry oil (P <0.01). Corn oil increased the mRNA abundance of cGRP compared to poultry oil (P <0.01). Compared with group fed corn-oil or poultry-oil diets, IMLs had lower concentration of cAMP and lower bioactivity of adenylyl cyclase (AC) of chickens supplemented with fish oil on 21 d and 42 d of age. Meanwhile, corn oil increased cAMP level and AC bioactivity. Taken together, these data show a modulatory role for cGRP in the interaction between different type of oils and T-cell differentiation and IL-2 bioactivity of IMLs in chickens, which suggests that AC and cAMP signalling involved the intestinal mucosal immune responses.

The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in γδ T cells in large intestinal mucosa

Oral tolerance has previously been shown effective in preventing several immune-mediated disorders in animal models. The aims of this study were to investigate the effect of oral colitis-extracted proteins (CEP) on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice and to explore the relative role of the intestinal mucosal gammadelta T cells. The effect of five low oral doses of CEP on colitis was evaluated by clinical manifestation and histological lesions. Serum cytokines were measured by enzyme-linked immunosorbent assay. The percentages of the intestinal mucosal gammadelta T cells were evaluated by flow cytometry. CEP-fed colitis mice showed less severe symptoms and histological injury than bovine serum albumin (BSA)-fed control mice. Tolerized mice developed an increase in TGF-beta1 and no change in IFN-gamma serum levels. Increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in small intestinal mucosal lymphocytes and no quantitative change in large intestinal mucosal lymphocytes were demonstrated in colitis mice compared to untreated mice. The proportions of TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes from CEP-fed colitis mice were significantly higher compared to BSA-fed controls. The disease activity index negatively correlated with the percentages of large intestinal mucosal gammadelta T cells. Furthermore, mucosal repair in repair-period mice was also accompanied by increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes. Improvement of DSS-induced colitis that resulted from oral administration of colitis-extracted proteins is associated with an increase in gammadelta T cells in large intestinal mucosa.

Toxic, Immunostimulatory and Antagonist Gluten Peptides in Celiac Disease

Celiac disease (CD) is an increasingly diagnosed, permanent autoimmune enteropathy, triggered, in susceptible individuals, by the ingestion of gluten, the alcohol - soluble protein fraction of some cereals, such as wheat, rye and barley. The main protein of wheat gluten is called gliadin, the similar proteins of rye and barley are secalin and hordein, respectively. Approximately 96% of CD patients express the HLA molecule DQ2, while the remainder mostly express the less common haplotype DQ8, reflecting the pivotal role of these molecules in the pathogenesis of CD. Because of their aminoacid sequence and tri-dimensional structure, gluten peptides selectively bind to these HLA alleles present on the surface of antigen presenting cells and then they are presented to the T lymphocytes in intestinal mucosa, thus starting the inflammatory immune response. CD is defined by the characteristic histological changes of small bowel mucosa: villous atrophy, crypts hyperplasia and T cells infiltration of the lamina propria, along with the increase of the number of intra-epithelial lymphocytes. The withdrawal of the gluten- containing food from the diet determines a complete recovery of the intestinal mucosa, whereas the reintroduction causes a relapse of the disease. This review focuses on the description of gluten peptides that elicit the mucosal immune response via the activation of innate and adaptive immunity in CD. It also describes the antagonist gluten peptides, obtained by artificial modification of gluten T epitopes or naturally occurring in the alcohol protein fraction of a cultivar of durum wheat, able to immuno-modulate the pathogenic immune response of CD.

Specific overexpression of IL-7 in the intestinal mucosa: the role in intestinal intraepithelial lymphocyte development

IL-7 plays a crucial role in controlling T cell development and homeostasis. Since IL-7 may be derived from extraintestinal sources, and exogenous IL-7 broadly affects lymphoid populations, the actions of epithelial cell (EC)-derived IL-7 are not fully understood. The effect of intestinal specific expression of IL-7 on intestinal mucosal lymphocytes was investigated by using an IL-7 transgenic mouse model. We generated an intestinal EC-specific overexpressing IL-7 transgenic mouse model (IL-7(vill)) and compared their phenotype and function to wild-type C57BL/6J mice. EC-derived IL-7 overexpression was found to be exclusively in the small and large intestine. Numbers and subtypes of mucosal lymphocytes, including intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL), significantly changed in IL-7(vill) mice. From a functional standpoint, IEL proliferation also significantly increased in IL-7(vill) mice. IEL cytokine expression significantly changed in both T cell receptor (TCR)-alphabeta(+) and TCR-gammadelta(+) IEL subpopulations, including a significant increase in IFN-gamma and TNF-alpha as well as an increase in keratinocyte growth factor expression. EC expression of CD103 (integrin alpha(E)beta(7)), the ligand of E-cadherin, markedly upregulated and may account for a mechanism of the massive expansion of IEL in transgenic mice. Systemic lymphoid populations did not change in transgenic mice. IL-7 overexpression by intestinal EC significantly affected IEL phenotype and function. These results offer insight into the role of IL-7 in IEL development and suggest a critical role of EC-derived expression of IL-7 in the phenotype and function of IEL.

Intestinal mucosal lymphocyte activation and effective response in inflammatory bowel disease

Intestinal mucosal lymphocyte activation and effective response in inflammatory bowel disease

Modulation of intestinal mucosal immunity by dietary polyunsaturated fatty acids in chickens

This study was undertaken to investigate the effects of dietary polyunsaturated fatty acids (PUFA) on intestinal immune responses and cytokines secretions in chickens at nutrition-immunity level. The proportion of CD3+CD8+ lymphocytes of intestinal mucosa in CO group was higher on d 21 than that in FO (p < 0.01) and PO (p < 0.05) group. The proportion of CD3+CD4+ lymphocytes of FO group was greatly significantly higher on d 21, relative to PO or CO group. The FO treatment enhanced the sIgA concentration in jejunum on d 42, compared with CO and PO group. Fish oil and corn oil had similar effects on enhancing IL-2 secretion of PBMC, and converse effects on IL-4 secretion. Compared with PO group, chickens supplemented with fish oil or corn oil had greater concentration of intestinal mucosal membrane phospholipids on d 21 and d 42. In conclusion, the changes of intestinal lymphocytes membrane phospholipids in FO or CO group would modulate lipid second messengers. The changes of CD expression would affect sIgA secretion of intestinal lymphocytes. Diet supplemented with corn oil or fish oil can affect cytokines secretion of PBMC in chickens, which works on systemic and mucosal immune response.

Interleukin-21 enhances T-helper cell type I signaling and interferon-γ production in Crohn’s disease

T-helper (Th)1 cells play a central role in the pathogenesis of tissue damage in Crohn's disease (CD). Interleukin (IL)-12/STAT4 signaling promotes Th1 cell commitment in CD, but other cytokines are needed to maintain activated Th1 cells in the mucosa. In this study, we examined the expression and role of IL-21, a T-cell-derived cytokine of the IL-2 family; in tissues and cells isolated from patients with inflammatory bowel disease. IL-21 was examined by Western blotting in whole mucosa and lamina propria mononuclear cells (LPMCs) from patients with CD, ulcerative colitis (UC), and controls. We also examined the effects of exogenous IL-12 on IL-21 production, as well as the effects of blocking IL-21 with an IL-21-receptor Ig fusion protein. Interferon (IFN)-gamma was measured in the culture supernatants by enzyme-linked immunosorbent assay, and phosphorylated STAT4 and T-bet were examined by Western blotting. IL-21 was detected in all samples, but its expression was higher at the site of disease in CD in comparison with UC and controls. Enhanced IL-21 was seen in both ileal and colonic CD and in fibrostenosing and nonfibrostenosing disease. IL-12 enhanced IL-21 in normal lamina propria lymphocytes through an IFN-gamma-independent mechanism, and blocking IL-12 in CD LPMCs decreased anti-CD3-stimulated IL-21 expression. Neutralization of IL-21 in CD LPMC cultures decreased phosphorylated STAT4 and T-bet expression, thereby inhibiting IFN-gamma production. Our data suggest that IL-21 contributes to the ongoing Th1 mucosal response in CD.

Decrease of interleukin-7-induced apoptosis of IL-7 receptor+ intestinal mucosal lymphocytes in chronic inflamaed colonic mucosa of ulcerative colitis

Decrease of interleukin-7-induced apoptosis of IL-7 receptor+ intestinal mucosal lymphocytes in chronic inflamaed colonic mucosa of ulcerative colitis

Decrease of interleukin-7-induced apoptosis of IL-7 receptor+ intestinal mucosal lymphocytes in chronic inflamaed colonic mucosa of ulcerative colitis

Decrease of interleukin-7-induced apoptosis of IL-7 receptor+ intestinal mucosal lymphocytes in chronic inflamaed colonic mucosa of ulcerative colitis

Interleukin-18 and Crohn’s Disease

The etiology and pathogenesis of inflammatory bowel disease remains an area under intense investigation. Crohn’s disease (CD) is characterized by a marked accumulation of activated Th1 type CD4+ T cells and macrophages in inflamed intestinal mucosa. IL-18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4+ T cells by inducing interferon-γ. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucosal lymphocytes in human CD and murine CD model.