Victoria Male

Sir Henry Dale Fellow

Research area

Innate lympoid cell biology.

Research programme

Immune regulation

Research summary

The natural killer (NK) cells that circulate in the blood are immune cells that defend the body against viruses and cancer. There are also organ-specific NK cells that differ from those in the blood and have special roles in their home organs. In the past, I have investigated the NK cells that are found in the human uterus and that help the placenta to invade into the lining of the uterus in the first trimester of pregnancy. My new research group at the Institute of Immunity and Transplantation focusses on NK cells in the liver.

Recently, a number of groups have identified liver-resident NK cells (which are sometimes considered to be helper ILC1) in mice. The first major paper to come out of my research group examined peripheral blood and intrahepatic NK cells from recipients of HLA-mismatched liver transplants to show that an equivalent, liver-resident NK cell is also present in humans. We further showed that the precursors of liver-resident NK cells can be recruited from the blood during adult life and defined conditions that can convert circulating NK cells to cells with a liver-resident phenotype. We are now working to define the function of these cells, both in humans and in mice, and how they may be involved in non-alcoholic fatty liver disease.

Publications

Selected publications

Kostrzewski T, Borg AJ, Meng Y, Filipovic I, Male V, Wack A, DiMaggio PA, Brady HJM. Multiple levels of control determine how E4bp4/Nfil3 regulates NK cell development. J Immunol. 2018;200:1370-1380
Male V, Stegmann KA, Easom NJ, Maini MK. Natural Killer Cells in Liver Disease. Semin Liver Dis. 2017;37:198-209
Cuff AO, Male V. Conventional NK cells and ILC1 are partially ablated in the livers of Ncr1 (iCre)Tbx21 (fl/fl) mice. Wellcome Open Res. 2017;2:39
Pallett LJ, Davies J, Colbeck EJ, Robertson F, Hansi N, Easom NJW, Burton AR, Stegmann KA, Schurich A, Swadling L, Gill US, Male V, Luong T, Gander A, Davidson BR, Kennedy PTF, Maini MK. IL-2(high) tissue-resident T cells in the human liver: Sentinels for hepatotropic infection. J Exp Med. 2017;214:1567-1580
Male V, Brady HJM. Murine thymic NK cells: A case of identity. Eur J Immunol. 2017;47:797-799
Male V. Liver-Resident NK Cells: The Human Factor. Trends Immunol. 2017;38:307-309
Irshad S, Flores-Borja F, Lawler K, Monpenny J, Evans R, Male V, Gordon P, Cheung A, Gazinska P, Noor F, Wong F, Grigoriadis A, Fruhwirth GO, Barber PR, Woodman N, Patel D, Rodriguez-Justo M, Owen J, Martin SG, Pinder SE, Gillet CE, Poland SP, Ameer-Beg S, McCaughan F, Carlin LM, Hasan U, Withers DR, Lane P, Vojnovic B, Quexada SA, Ellis P, Tutt AN, Ng T. RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Res. 2017;77:1083-1096
Robertson F, Male V, Wright G, Fuller B, Davidson B. Recruitment of inflammatory monocytes after liver transplantation and correlation with clinical outcome. Lancet. 2017;389,S84
Cuff AO, Robertson FP, Stegmann KA, Pallett LJ, Maini MK, Davidson BR, Male V. Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation. J Immunol. 2016;197:4283-4291
Stegmann KA, Robertson F, Hansi N, Gill U, Pallant C, Christophides T, Pallett LJ, Peppa D, Dunn C, Fusai G, Male V, Davidson BR, Kennedy P, Maini MK. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver. Sci Rep. 2016;6:26157.