A circulating subset of iNKT cells mediates antitumor and antiviral immunity

被引：30

作者：

Cui, Guangwei ^{[1
]}

Shimba, Akihiro ^{[1
,2
]}

Jin, Jianshi ^{[3
]}

Ogawa, Taisaku ^{[3
]}

Muramoto, Yukiko ^{[4
]}

Miyachi, Hitoshi ^{[5
]}

Abe, Shinya ^{[1
]}

Asahi, Takuma ^{[1
,6
]}

Tani-Ichi, Shizue ^{[1
,2
]}

Dijkstra, Johannes M. ^{[7
]}

Iwamoto, Yayoi ^{[8
]}

Kryukov, Kirill ^{[9
,10
]}

Zhu, Yuanbo ^{[1
]}

Takami, Daichi ^{[1
,11
]}

Hara, Takahiro ^{[1
]}

Kitano, Satsuki ^{[5
]}

Xu, Yan ^{[12
]}

Morita, Hajime ^{[8
]}

Zhang, Moyu ^{[8
]}

Zreka, Lynn ^{[8
]}

Miyata, Keishi ^{[13
]}

Kanaya, Takashi ^{[14
]}

Okumura, Shinya ^{[15
]}

Ito, Takashi ^{[15
]}

Hatano, Etsuro ^{[15
]}

Takahashi, Yoshimasa ^{[16
]}

Watarai, Hiroshi ^{[17
]}

Oike, Yuichi ^{[13
]}

Imanishi, Tadashi ^{[9
]}

Ohno, Hiroshi ^{[14
]}

Ohteki, Toshiaki ^{[18
]}

Minato, Nagahiro ^{[12
]}

Kubo, Masato ^{[19
,20
]}

Hollander, Georg A. ^{[21
,22
,23
,24
]}

Ueno, Hideki ^{[8
]}

Noda, Takeshi ^{[4
]}

Shiroguchi, Katsuyuki ^{[3
]}

Ikuta, Koichi ^{[1
]}

机构：

[1] Kyoto Univ, Inst Life & Med Sci, Dept Virus Res, Lab Immune Regulat, Kyoto, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Human Hlth Sci, Kyoto, Japan

[3] RIKEN Ctr Biosyst Dynam Res BDR, Lab Predict Cell Syst Dynam, Osaka, Japan

[4] Kyoto Univ, Inst Life & Med Sci, Dept Virus Res, Lab Ultrastruct Virol, Kyoto, Japan

[5] Kyoto Univ, Inst Life & Med Sci, Reprod Engn Team, Kyoto, Japan

[6] Kyoto Univ, Grad Sch Med, Kyoto, Japan

[7] Fujita Hlth Univ, Inst Comprehens Med Sci, Toyoake, Aichi, Japan

[8] Kyoto Univ, Grad Sch Med, Dept Immunol, Kyoto, Japan

[9] Tokai Univ, Dept Mol Life Sci, Biomed Informat Lab, Hiratsuka, Kanagawa, Japan

[10] Natl Inst Genet, Dept Informat, Biol Networks Lab, Shizuoka, Japan

[11] Kyoto Univ, Grad Sch Pharmaceut Sci, Kyoto, Japan

[12] Kyoto Univ, Med Innovat Ctr, Grad Sch Med, Kyoto, Japan

[13] Kumamoto Univ, Grad Sch Med Sci, Dept Mol Genet, Kumamoto, Japan

[14] RIKEN Ctr Integrat Med Sci IMS, Lab Intestinal Ecosyst, Yokohama, Kanagawa, Japan

[15] Kyoto Univ, Grad Sch Med, Dept Surg, Div Hepatobiliary Pancreat Surg & Transplantat, Kyoto, Japan

[16] Natl Inst Infect Dis, Res Ctr Drug & Vaccine Dev, Tokyo, Japan

[17] Kanazawa Univ, Fac Med, Inst Med Pharmaceut & Hlth Sci, Dept Immunol & Stem Cell Biol, Kanazawa, Ishikawa, Japan

[18] Tokyo Med & Dent Univ, Med Res Inst, Dept Biodef Res, Tokyo, Japan

[19] RIKEN Ctr Integrat Med Sci IMS, Lab Cytokine Regulat, Yokohama, Kanagawa, Japan

[20] Tokyo Univ Sci, Res Inst Biomed Sci, Div Mol Pathol, Chiba, Japan

[21] Univ Oxford, Weatherall Inst Mol Med, Oxford, England

[22] Univ Basel, Dept Biomed, Pediat Immunol, Basel, Switzerland

[23] Univ Childrens Hosp Basel, Basel, Switzerland

[24] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland

来源：

SCIENCE IMMUNOLOGY | 2022年 / 7卷 / 76期

基金：

日本学术振兴会;

关键词：

INVARIANT NKT CELLS; NATURAL-KILLER; T-CELLS; IFN-GAMMA; EXPRESSION; MICE; LUNG; HOMEOSTASIS; PROVIDES; ABSENCE;

D O I：

10.1126/sciimmunol.abj8760

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Invariant natural killer T (iNKT) cells are a group of innate-like T lymphocytes that recognize lipid antigens. They are supposed to be tissue resident and important for systemic and local immune regulation. To investigate the heterogeneity of iNKT cells, we recharacterized iNKT cells in the thymus and peripheral tissues. iNKT cells in the thymus were divided into three subpopulations by the expression of the natural killer cell receptor CD244 and the chemokine receptor CXCR6 and designated as C0 (CD244(-)CXCR6(-)), C1 (CD244(-)CXCR6(+)), or C2 (CD244(+)CXCR6(+)) iNKT cells. The development and maturation of C2 iNKT cells from C0 iNKT cells strictly depended on IL-15 produced by thymic epithelial cells. C2 iNKT cells expressed high levels of IFN-. and granzymes and exhibited more NK cell-like features, whereas C1 iNKT cells showed more T cell-like characteristics. C2 iNKT cells were influenced by the microbiome and aging and suppressed the expression of the autoimmune regulator AIRE in the thymus. In peripheral tissues, C2 iNKT cells were circulating that were distinct from conventional tissue-resident C1 iNKT cells. Functionally, C2 iNKT cells protected mice from the tumor metastasis of melanoma cells by enhancing antitumor immunity and promoted antiviral immune responses against influenza virus infection. Furthermore, we identified human CD244(+)CXCR6(+) iNKT cells with high cytotoxic properties as a counterpart of mouse C2 iNKT cells. Thus, this study reveals a circulating subset of iNKT cells with NK cell-like properties distinct from conventional tissue-resident iNKT cells.

引用

页数：19

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