Loading...
Please wait, while we are loading the content...
This information is current as Development and Functions Role of SHIP 1 in Invariant NKT Cell
| Content Provider | Semantic Scholar |
|---|---|
| Author | Anderson, Courtney K. Salter, Alexander I. Toussaint, Leon E. Reilly, Emma Fugère, Céline Srivastava, Neetu Kerr, William G. Brossay, Laurent |
| Copyright Year | 2015 |
| Abstract | SHIP1 is a 59-inositol phosphatase known to negatively regulate the signaling product of the PI3K pathway, phosphatidylinositol (3–5)-trisphosphate. SHIP1 is recruited to a large number of inhibitory receptors expressed on invariant NK (iNKT) cells. We hypothesized that SHIP1 deletion would have major effects on iNKT cell development by altering the thresholds for positive and negative selection. Germline SHIP1 deletion has been shown to affect T cells as well as other immune cell populations. However, the role of SHIP1 on T cell function has been controversial, and its participation on iNKT cell development and function has not been examined. We evaluated the consequences of SHIP1 deletion on iNKT cells using germline-deficient mice, chimeric mice, and conditionally deficient mice. We found that T cell and iNKT cell development are impaired in germline-deficient animals. However, this phenotype can be rescued by extrinsic expression of SHIP1. In contrast, SHIP1 is required cell autonomously for optimal iNKT cell cytokine secretion. This suggests that SHIP1 calibrates the threshold of iNKT cell reactivity. These data further our understanding of how iNKT cell activation is regulated and provide insights into the biology of this unique cell lineage. N atural killer T cells are a heterogeneous subset of innate lymphocytes that express NK cell markers in addition to a TCR. There are multiple functionally distinct categories of NKT cells, including invariant NKT (iNKT) cells, also known as type I NKT cells (1, 2). iNKT cells represent a small fraction of mature T cells within the thymus, spleen, and lymph nodes. However, iNKT cells also accumulate in non-lymphoid organs, including the blood, liver, and gut. In mice, iNKT cells make up a robust population within the liver, ranging between 25 and 40% of the lymphocytes (3). iNKT cell development occurs in the thymus from the same precursors as conventional T cells but diverges during positive selection (1, 2, 4). Although conventional T cells are selected and restricted by classical MHC peptide Ags presented by thymic cortical epithelial cells, iNKT cells are selected by CD4 + CD8 + double positive (DP) cortical thymocytes that express CD1d (1, 2). CD1d is a nonclas-sical MHC class I–like molecule that preferentially binds glyco-lipid Ags (1, 2). iNKT cells are able to recognize presented glycolipid Ags because of their unique semi-invariant TCR, which consists of an invariant V a 14-J a 18 chain that preferentially dimerizes with a limited number of b-chains, mainly V b … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2015/07/30/jimmunol.1500567.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/195/5/2149.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2015/07/30/jimmunol.1500567.full.pdf?with-ds=yes |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
