• BMB Reports
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• 제49권1호
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• pp.11-17
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• 2016

The gastrointestinal tract forms the largest surface in our body with constantly being exposed to various antigens, which provides unique microenvironment for the immune system in the intestine. Accordingly, the gut epithelium harbors the most T lymphocytes in the body as intraepithelial lymphocytes (IELs), which are phenotypically and functionally heterogeneous populations, distinct from the conventional mature T cells in the periphery. IELs arise either from pre-committed thymic precursors (natural IELs) or from conventional CD4 or CD8αβ T cells in response to peripheral antigens (induced IELs), both of which commonly express CD8α homodimers (CD8αα). Although lineage commitment to either conventional CD4 T helper (Th) or cytotoxic CD8αβ T cells as well as their respective co-receptor expression are mutually exclusive and irreversible process, CD4 T cells can be redirected to the CD8 IELs with high cytolytic activity upon migration to the gut epithelium. Recent reports show that master transcription factors for CD4 and CD8 T cells, ThPOK (Th-inducing BTB/POZ-Kruppel-like factor) and Runx3 (Runt related transcription factor 3), respectively, are the key regulators for re-programming of CD4 T cells to CD8 lineage in the intestinal epithelium. This review will focus on the unique differentiation process of IELs, particularly lineage re-commitment of CD4 IELs. [BMB Reports 2016; 49(1): 11-17]

• Molecules and Cells
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• 제42권4호
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• pp.313-320
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• 2019

Intraepithelial lymphocytes (IELs) develop through the continuous interaction with intestinal antigens such as commensal microbiome and diet. However, their respective roles and mutual interactions in the development of IELs are largely unknown. Here, we showed that dietary antigens regulate the development of the majority of $CD8{\alpha}{\beta}$ IELs in the small intestine and the absence of commensal microbiota particularly during the weaning period, delay the development of IELs. When we tested specific dietary components, such as wheat or combined corn, soybean and yeast, they were dependent on commensal bacteria for the timely development of diet-induced $CD8{\alpha}{\beta}$ IELs. In addition, supplementation of intestinal antigens later in life was inefficient for the full induction of $CD8{\alpha}{\beta}$ IELs. Overall, our findings suggest that early exposure to commensal bacteria is important for the proper development of dietary antigen-dependent immune repertoire in the gut.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제17권3호
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• pp.186-190
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• 2014

Lymphocytic gastritis (LG) is a rare subtype of chronic gastritis. It is defined as dense proliferation of intraepithelial lymphocytes (IELs) more than 25 lymphocytes per 100 epithelial cells. The known major causes of LG are celiac disease and Helicobacter pylori infection. H. pylori associated LG (HpLG) has more enhanced cytotoxic and apoptotic tendencies than chronic H. pylori gastritis. A 12-year-old girl with postprandial epigastric pain was diagnosed HpLG on endoscopic biopsy. After the 1st eradication therapy, H. pylori bacilli were still found, and urea breathing test was positive. Although the endoscopic finding was partially improved, clinical symptoms and histologic finding were persisted. We could achieve the improvement of clinical symptoms and disappearance of IELs after the 2nd eradication. The discordant of histopathologic and endoscopic improvement occurred after the 1st eradication therapy of HpLG. Therefore the clinical and histopathologic evaluation should be considered as well as endoscopic findings.

• 대한의생명과학회지
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• 제5권1호
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• pp.109-118
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• 1999

저자들은 호르텐스극구흡충을 실험적으로 흰쥐 (Sprague Dawley)에 감염시켰을때 장상피 내 림프구 (intraepithelial lymphocytes: IEL)의 증감여부를 관찰하였다. 즉, 피낭유충을 경 구 감염시킨 다음 1주일부터 8주일까지 격주별로 소장점막에서 IEL의 수치, 융모/선와의 비 (villus/crypt ratio)등을 현미경적으로 관찰하였다. 감염 흰쥐는 격주별로 희생시켰으며 소장의 십이지장과 공장부위의 조직을 획득하여 조직 절편을 제작하였고, Hematoxylin-eosin 및 Giemsa 염색을 실시한 후 IEL 수, 위치의 변동을 현미경적으로 관찰하였다. 융모 위축과 선와 증식 , V/C ratio의 감소를 특징으로 하는 장병변은 감염 1주일 경과한 소장에서 가장 심하였으며 이 병변은 8주일까지 계속되고 있었다. IEL은 감염 1주일에 급속하게 감소하였다가 서서히 증가하다가 8주일 때에는 다소 감소하는 결과를 보였다. 대조군에서 IEL은 대부분 장상피층의 기저부에 위치하였으나, 감염 초기에는 많은 IEL이 장상피세포의 핵주변부와 상층부에 분포하는 것이 특이하였다. 이와 같이 호르텐스극구흡충 감염시 나타나는 IEL수 및 위치의 변동은 장병변의 진행과정과 관련이 있음을 알 수 있었다.

• Parasites, Hosts and Diseases
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• 제40권3호
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

• Animal cells and systems
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• 제11권2호
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• pp.155-160
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• 2007

The skin of the Korean bullheads, Pseudobagrus brevicorpus and P. koreanus, is composed of epidermis, dermis and subcutis. The epidermis has three layers, the outermost layer, middle layer and stratum germinativum. The epidermis consists of two types of gland cells, an unicellular mucous cell of sulfomucin and a large club cell having sometimes two nuclei. The epidermis has numerous intraepithelial blood vessels in P. brevicorpus but not at all in P. koreanus. Lymphatic spaces containing lymphocytes are well developed in mainly the stratum germinativum. The dermis lacks scales and consists mostly of bundles of coarse collagen fibers. The collagen bundles are arranged in parallel to each other in the dorsum and lateral region toward the dorsum, but vertically at intervals in the abdomen and lateral region toward the abdomen. Considering this unique skin structure, the two species are likely to exercise cutaneous respiration as a dual respiratory system to overcome hypoxic conditions which frequently occurs in their habitats.

• Parasites, Hosts and Diseases
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• 제52권1호
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• pp.27-33
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• 2014

Mucosal immune responses against Pygidiopsis summa (Trematoda: Heterophyidae) infection were studied in ICR mice. Experimental groups consisted of group 1 (uninfected controls), group 2 (infection with 200 metacercariae), and group 3 (immunosuppression with Depo-Medrol and infection with 200 metacercariae). Worms were recovered in the small intestine at days 1, 3, 5, and 7 post-infection (PI). Intestinal intraepithelial lymphocytes (IEL), mast cells, and goblet cells were counted in intestinal tissue sections stained with Giemsa, astra-blue, and periodic acid-Schiff, respectively. Mucosal IgA levels were measured by ELISA. Expulsion of P. summa from the mouse intestine began to occur from days 3-5 PI which sustained until day 7 PI. The worm expulsion was positively correlated with proliferation of IEL, mast cells, goblet cells, and increase of IgA, although in the case of mast cells significant increase was seen only at day 7 PI. Immunosuppression suppressed all these immune effectors and inhibited worm reduction in the intestine until day 7 PI. The results suggested that various immune effectors which include IEL, goblet cells, mast cells, and IgA play roles in regulating the intestinal mucosal immunity of ICR mice against P. summa infection.

• Parasites, Hosts and Diseases
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• 제32권4호
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• pp.215-222
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• 1994

요코가와흡충 감염시 장상피내 림프구(inkaepithelial Iympho%rotes: IEL)의 증감과 장 병변의 상관관계를 알아보기 위하여 흰쥐(Sprague-Dawley)에 피낭유충을 실험 감염시킨 다음 5일 부터 70일까지 소장 점막에서 IEL 수와 위치, V/C ratio(villus/crypt ratio; 융모/선와의 비) 등을 관찰하였다. 피낭유충은 은어(Plecoglossus altivelis)에서 획득하여 흰쥐 15마리에 각각 3,000개씩 경구 감염시켰고 동일계 흰쥐 3마리를 비감염 대조군으로 사용하였다 감염 5일, 10일, 15일, 24 일 및 70일에 각각 3마리씩 희생시킨 다음 소장 여러 부위에서 조직을 획득하여 절편으로 제작하였고, Giemsa 염색한 후, 병리학적 관찰과 함께 IEL수 및 위치의 변동을 경시적으로 관찰하였다. 응모 위축과 선와 증식. V/C ratio의 감소 등을 특징으로 하는 장병변은 감염 후 5일에서 15일 사이에 가장 심하였으며 감염 24일째부터는 점차 회복되었다. IEL은 감염 초기에 일시적으로 증가하였으나, 장병변이 진행되면서 대조군보다 감소하였다가, 장병변의 회복과 함께 다시 증가하였다 대조군에서 IEL은 대부운 장상피층의 기저부에 위치하였으나, 감염 초기에는 많은 IEL이 장상괴세포의 핵주변부와 상층부에 분포하는 점이 특이하였다 이와 같이 요코가와흡충 감염시 나타나는 IEL수 및 위치의 변동은 장병변의 진행 과정과 밀접한 관련이 있음을 알 수 있었다.

• Asian-Australasian Journal of Animal Sciences
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• 제29권10호
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• pp.1515-1521
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• 2016

Anethole and garlic have an immune modulatory effects on avian coccidiosis, and these effects are correlated with gene expression changes in intestinal epithelial lymphocytes (IELs). In this study, we integrated gene expression datasets from two independent experiments and investigated gene expression profile changes by anethole and garlic respectively, and identified gene expression signatures, which are common targets of these herbs as they might be used for the evaluation of the effect of plant herbs on immunity toward avian coccidiosis. We identified 4,382 and 371 genes, which were differentially expressed in IELs of chickens supplemented with garlic and anethole respectively. The gene ontology (GO) term of differentially expressed genes (DEGs) from garlic treatment resulted in the biological processes (BPs) related to proteolysis, e.g., "modification-dependent protein catabolic process", "proteolysis involved in cellular protein catabolic process", "cellular protein catabolic process", "protein catabolic process", and "ubiquitin-dependent protein catabolic process". In GO analysis, one BP term, "Proteolysis", was obtained. Among DEGs, 300 genes were differentially regulated in response to both garlic and anethole, and 234 and 59 genes were either up- or down-regulated in supplementation with both herbs. Pathway analysis resulted in enrichment of the pathways related to digestion such as "Starch and sucrose metabolism" and "Insulin signaling pathway". Taken together, the results obtained in the present study could contribute to the effective development of evaluation system of plant herbs based on molecular signatures related with their immunological functions in chicken IELs.

• Asian-Australasian Journal of Animal Sciences
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• 제18권9호
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• pp.1320-1325
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• 2005

A 2${\times}$3 factorial arrangement of treatments was used to determine the effects of olaquindox and cyadox on immune response of Landrace${\times}$Large-White geld piglets that had been orally given 10$^{10}$ CFU of Escherichia coli (E. coli, O$_{139}$:K$_{88}$). Factors included (1) E. coli inoculation or control, and (2) no antimicrobials, 100 mg/kg olaquindox and 100 mg/kg cyadox in the basal diet respectively. E. coli inoculums were orally administered 7 days after the diets were supplemented with olaquindox and cyadox. The effects of the two antimicrobials were assessed in terms of: (1) average daily gain (ADG), (2) systemic immune response (the number of white blood cells and lymphocytes, leukocyte bactericidal capacity, lymphocyte proliferation response to PHA, immunoglobulin concentrations, and total serous hemolytic complement activity), and (3) intestinal mucosal immunity including the number of intraepithelial lymphocytes (IELs) and immunoglobulin A secreting cells (ASCs) in the intestinal lamina propria. E. coli inoculation reduced ADG (p<0.05) during the period of d 0 to d 14 after the challenge while the antimicrobial supplementations improved ADG (p<0.01) during the experiment. ADG in cyadox-supplemented pigs was higher (p<0.05) than that in olaquindox-supplemented pigs. The antimicrobials decreased IEL and ASC counts in the jejunum and ileum (p<0.01) while E. coli inoculation caused them to increase (p<0.01). Jejunal ASCs in the cyadox-supplemented pigs were lower (p<0.05) than those in the olaquindox-supplemented. E. coli elicited increase (p<0.05) in white blood cell counts, leukocyte bactericidal capacity, lymphocyte proliferation rate, serous IgA concentrations, and serous hemolytic complement activity. The antimicrobials decreased the measured systemic immune parameters, but not significantly (p>0.05). The data suggest that olaquindox and cyadox suppress E. coli-induced immune activation, especially intestinal mucosal immune activation, which may be involved in the observed growth promotion.