Asia and International Law—Common Ground and Regional Diversity

From a conceptual viewpoint, the legal universe has found its almost perfect configuration in our time. Almost all of the peoples of the world are members of the United Nations and as such are entitled to co-operate in shaping the direction and content of policies at the global level. Before World War II, and even a considerable time after the horrendous events unleashed by that war, many nations had no say in international matters. They were placed under colonial rule, which meant that their voices were not heard—or heard only through the mediation of the powers that acted as their wards and guardians. That situation of structural discrimination has changed dramatically. All the peoples of the world have reached sovereign statehood and have been admitted to the world forum.Peer Reviewe

Die Zukunft des Völkerrechts

The international legal order today constitutes a truly universal legal system. It has received guiding principles through the United Nations Charter: ever since this ‘Constitution for the world’ began operating, sovereign equality of states, self‑determination of peoples, and human rights have been key components of this architecture, which has reached a state of ‘conceptual unity’ belying the talk of ‘fragmentation’ of international law that so fascinated scholars in their debates only a short while ago. The great peace treaties of 1648, 1815, and 1919, as Euro‑centric instruments influenced by the interests of the dominant powers, could not bring about a peaceful world order. After World War II, it was, in particular, the inclusion of the newly independent states in the legislative processes that has conferred an unchallenged degree of legitimacy on international law. Regrettably, its effectiveness has not kept pace with its normative growth. Some islands of stability can be identified. On the positive side, one can note a growing trend to entrust the settlement of disputes to formal procedures. Yet the integration of human rights in international law – a step of moral advancement that proceeds from the simple recognition that, precisely in the interest of world peace, domains of domestic and international matters cannot be separated one from the other as neatly as postulated by the classic doctrine of international law – has placed enormous obstacles before international law. It must be expected that the demand for more justice on the part of developing nations will subject the international legal order to even greater strain in the near future. Currently, chances are low that the issue of migration from the poorer South to the ‘rich’ North can be resolved

HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44⁺ Natural Killer Cells in Ulcerative Colitis

Background &amp; Aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated. Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764). Expression levels of HLA-DP on intestinal epithelial cells (IECs) in individuals with and without UC were quantified. Human intestinal 3-dimensional (3D) organoid cocultures with human NK cells were used to determine functional consequences of interactions between HLA-DP and NKp44. Results: These studies identified HLA-DPA1∗01:03-DPB1∗04:01 (HLA-DP401) as a risk haplotype and HLA-DPA1∗01:03-DPB1∗03:01 (HLA-DP301) as a protective haplotype for UC in European populations. HLA-DP expression was significantly higher on IECs of individuals with UC compared with controls. IECs in human intestinal 3D organoids derived from HLA-DP401pos individuals showed significantly stronger binding of NKp44 compared with HLA-DP301pos IECs. HLA-DP401pos IECs in organoids triggered increased degranulation and tumor necrosis factor production by NKp44+ NK cells in cocultures, resulting in enhanced epithelial cell death compared with HLA-DP301pos organoids. Blocking of HLA-DP401–NKp44 interactions (anti-NKp44) abrogated NK cell activity in cocultures. Conclusions: We identified an UC risk HLA-DP haplotype that engages NKp44 and activates NKp44+ NK cells, mediating damage to intestinal epithelial cells in an HLA-DP haplotype–dependent manner. The molecular interaction between NKp44 and HLA-DP401 in UC can be targeted by therapeutic interventions to reduce NKp44+ NK cell–mediated destruction of the intestinal epithelium in UC.</p