INAM plays a critical role in IFN-γ production by NK cells interacting with polyinosinic-polycytidylic acid-stimulated accessory cells.

Abstract

Polyinosinic-polycytidylic acid strongly promotes the antitumor activity of NK cells via TLR3/Toll/IL-1R domain-containing adaptor molecule 1 and melanoma differentiation-associated protein-5/mitochondrial antiviral signaling protein pathways. Polyinosinic-polycytidylic acid acts on accessory cells such as dendritic cells (DCs) and macrophages (Mφs) to secondarily activate NK cells. In a previous study in this context, we identified a novel NK-activating molecule, named IFN regulatory factor 3-dependent NK-activating molecule (INAM), a tetraspanin-like membrane glycoprotein (also called Fam26F). In the current study, we generated INAM-deficient mice and investigated the in vivo function of INAM. We found that cytotoxicity against NK cell-sensitive tumor cell lines was barely decreased in Inam(-/-) mice, whereas the number of IFN-γ-producing cells was markedly decreased in the early phase. Notably, deficiency of INAM in NK and accessory cells, such as CD8α(+) conventional DCs and Mφs, led to a robust decrease in IFN-γ production. In conformity with this phenotype, INAM effectively suppressed lung metastasis of B16F10 melanoma cells, which is controlled by NK1.1(+) cells and IFN-γ. These results suggest that INAM plays a critical role in NK-CD8α(+) conventional DC (and Mφ) interaction leading to IFN-γ production from NK cells in vivo. INAM could therefore be a novel target molecule for cancer immunotherapy against IFN-γ-suppressible metastasis.

• Authors: Jun Kasamatsu, Masahiro Azuma, Hiroyuki Oshiumi, Yuka Morioka, Masaru Okabe, Takashi Ebihara, Misako Matsumoto, Tsukasa Seya
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 10 Pg. 5199-207 (Nov 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 25320282 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• CD8 Antigens
• CD8alpha antigen
• INAM protein, mouse
• Membrane Glycoproteins
• Interferon-gamma
• Poly I-C

Topics

• Animals
• CD8 Antigens (genetics, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology, pathology)
• Cell Differentiation
• Cell Line, Tumor
• Dendritic Cells (drug effects, immunology, pathology)
• Gene Expression Regulation
• Interferon-gamma (genetics, immunology)
• Killer Cells, Natural (drug effects, immunology, pathology)
• Lung (drug effects, immunology, pathology)
• Lung Neoplasms (genetics, immunology, pathology)
• Lymphocyte Activation
• Macrophages (drug effects, immunology, pathology)
• Melanoma, Experimental (genetics, immunology, pathology)
• Membrane Glycoproteins (deficiency, genetics, immunology)
• Mice
• Mice, Knockout
• Neoplasm Metastasis
• Neoplasm Transplantation
• Poly I-C (pharmacology)
• Signal Transduction