scholarly journals Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection

2006 ◽  
Vol 342 (3) ◽  
pp. 782-790 ◽  
Author(s):  
Dina Montufar-Solis ◽  
Tomas Garza ◽  
Ba-Bie Teng ◽  
John R. Klein
Keyword(s):  
Intraepithelial Lymphocytes ◽  
Reovirus Infection ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Small Intestinal

scholarly journals The histone demethylase Kdm6b regulates the maturation and cytotoxicity of TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes

2022 ◽  
Author(s):  
Haohao Zhang ◽  
Yiming Hu ◽  
Dandan Liu ◽  
Zhi Liu ◽  
Ningxia Xie ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Surveillance ◽  
Intraepithelial Lymphocytes ◽  
Target Cells ◽  
Histone 3 ◽  
Intestinal Intraepithelial Lymphocytes ◽  
H3k27me3 Level ◽  
Small Intestinal ◽  
And Function ◽  
Cytotoxic Function

AbstractIntestinal intraepithelial lymphocytes (IELs) are distributed along the length of the intestine and are considered the frontline of immune surveillance. The precise molecular mechanisms, especially epigenetic regulation, of their development and function are poorly understood. The trimethylation of histone 3 at lysine 27 (H3K27Me3) is a kind of histone modifications and associated with gene repression. Kdm6b is an epigenetic enzyme responsible for the demethylation of H3K27Me3 and thus promotes gene expression. Here we identified Kdm6b as an important intracellular regulator of small intestinal IELs. Mice genetically deficient for Kdm6b showed greatly reduced numbers of TCRαβ+CD8αα+ IELs. In the absence of Kdm6b, TCRαβ+CD8αα+ IELs exhibited increased apoptosis, disturbed maturation and a compromised capability to lyse target cells. Both IL-15 and Kdm6b-mediated demethylation of histone 3 at lysine 27 are responsible for the maturation of TCRαβ+CD8αα+ IELs through upregulating the expression of Gzmb and Fasl. In addition, Kdm6b also regulates the expression of the gut-homing molecule CCR9 by controlling H3K27Me3 level at its promoter. However, Kdm6b is dispensable for the reactivity of thymic precursors of TCRαβ+CD8αα+ IELs (IELPs) to IL-15 and TGF-β. In conclusion, we showed that Kdm6b plays critical roles in the maturation and cytotoxic function of small intestinal TCRαβ+CD8αα+ IELs.

scholarly journals Lymphocyte Cc Chemokine Receptor 9 and Epithelial Thymus-Expressed Chemokine (Teck) Expression Distinguish the Small Intestinal Immune Compartment

2000 ◽  
Vol 192 (5) ◽  
pp. 761-768 ◽  
Author(s):  
Eric J. Kunkel ◽  
James J. Campbell ◽  
Guttorm Haraldsen ◽  
Junliang Pan ◽  
Judie Boisvert ◽  
...  
Keyword(s):  
Small Intestine ◽  
Immune Responses ◽  
Chemokine Receptor ◽  
Molecular Mechanisms ◽  
Seminal Fluid ◽  
Intraepithelial Lymphocytes ◽  
Small Subset ◽  
Cc Chemokine ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Small Intestinal

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4+ and CD8+ T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9+, and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9−. TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.

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