| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Erlich, Henry A. Trachtenberg, Elizabeth A. Lin, Lin Ma, Chao Targan, Stephan R. Rajalingam, Raja Aziz, Najib Yusung, Susy McGovern, Dermot P. B. Heath, James R. Braun, Jonathan Wei, Bo |
| Description |
Author Affiliation: Lin L ( Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095); Ma C ( Division of Physics, Mathematics and Astronomy, California Institute of Technology, Pasadena, CA 91125); Wei B ( Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095); Aziz N ( Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095); Rajalingam R ( Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095); Yusung S ( Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095); Erlich HA ( Children's Hospital Oakland Research Institute, Oakland, CA 94609); Trachtenberg EA ( Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305); Targan SR ( Translational Genomics Group, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, CA 90048); McGovern DP ( Translational Genomics Group, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, CA 90048); Heath JR ( Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095); Braun J ( Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095) |
| Abstract |
NK cells are innate immune cells known for their cytolytic activities toward tumors and infections. They are capable of expressing diverse killer Ig-like receptors (KIRs), and KIRs are implicated in susceptibility to Crohn's disease (CD), a chronic intestinal inflammatory disease. However, the cellular mechanism of this genetic contribution is unknown. In this study, we show that the 'licensing' of NK cells, determined by the presence of KIR2DL3 and homozygous HLA-C1 in host genome, results in their cytokine reprogramming, which permits them to promote CD4(+) T cell activation and Th17 differentiation ex vivo. Microfluidic analysis of thousands of NK single cells and bulk secretions established that licensed NK cells are more polarized to proinflammatory cytokine production than unlicensed NK cells, including production of IFN-γ, TNF- , CCL-5, and MIP-1ß. Cytokines produced by licensed NK augmented CD4(+) T cell proliferation and IL-17A/IL-22 production. Ab blocking indicated a primary role for IFN-γ, TNF- , and IL-6 in the augmented T cell-proliferative response. In conclusion, NK licensing mediated by KIR2DL2/3 and HLA-C1 elicits a novel NK cytokine program that activates and induces proinflammatory CD4(+) T cells, thereby providing a potential biologic mechanism for KIR-associated susceptibility to CD and other chronic inflammatory diseases. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1400093 |
| Journal |
The Journal of Immunology |
| Issue Number |
2 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cd4-positive T-lymphocytes Immunology Cytokines Killer Cells, Natural Receptors, Kir Metabolism Cell Differentiation Cell Proliferation Cells, Cultured Cluster Analysis Coculture Techniques Crohn Disease Blood Classification Flow Cytometry Hla-c Antigens Interferon-gamma Interleukin-17 Interleukin-6 Interleukins Lymphocyte Activation Receptors, Kir2dl3 Th17 Cells Tumor Necrosis Factor-alpha Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
