Shamima Begum should be repatriated by Britain, according to United Nations experts.
UN special rapporteurs have urged Britain to provide the 24-year-old with protection.
Begum, now 24, argued the decision was unlawful, in part because British officials failed to properly consider whether she was a victim of trafficking, an argument that was rejected by a lower court in February 2023.
The Court of Appeal in London rejected her appeal on Friday following an appeal in October.
UN special rapporteurs have urged Britain to protect Begum
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The statement was issued by the special rapporteurs on people trafficking, on contemporary slavery, on human rights while countering terrorism, on the sale and sexual exploitation of children, and on violence against women.
UN special rapporteurs said: "Begum remains stripped of her citizenship, vulnerable, and denied assistance and protection as a possible victim of trafficking.
"There is a credible suspicion that Ms Begum was recruited, transferred and then harboured for the purpose of sexual exploitation. Human trafficking is an international crime, a form of modern slavery.
"Protections owed to victims of trafficking and those at risk of trafficking, especially children, must be respected to be meaningful."
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In 2020, the Court of Appeal ruled that Begum should be allowed to return to Britain in order to fairly challenge the removal of her citizenship. But that decision was overturned by the Supreme Court the following year.
Begum's case has been the subject of heated debate between those who argue she willingly joined a terrorist group and others who say she was a child when she left or should face justice for any alleged crimes in Britain.
She left London in 2015, aged 15, and travelled with two school friends to Syria, where she married an Isis fighter and gave birth to three children, all of whom died as infants.
Begum has been in the al-Roj camp since 2019, with thousands of other foreign women and children.
British-born Shamima Begum from Bethnal Green in London, who joined Islamic State in Syria aged 15 in 2015
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One of Begum's lawyers Daniel Furner said: "I want to say that I'm sorry to Shamima and to her family that, after five years of fighting, she still hasn't received justice in a British court and to promise her and promise the government that we are not going to stop fighting until she does get justice and until she is safely back home."
Sajid Javid, the Home Secretary who took the decision to deprive Ms Begum of her British citizenship, said afterwards: "I welcome the court ruling, which has again upheld my decision to remove an individual's citizenship on national security grounds.
"This is a complex case but Home Secretaries should have the power to prevent anyone entering our country who is assessed to pose a threat to it."
