Reproductive Entanglements in Times of War: Transnational Gestational Surrogacy in Ukraine and Beyond.

Until early 2022, within the global fertility industry, Ukraine was one of the most important destinations for reproductive travel worldwide, particularly specializing in gestational surrogacy for international intended parents. Already weakened by the COVID-19 pandemic and related restrictions, the surrogacy market, and here especially surrogates and intended parents, was strongly affected by the Russian invasion in February 2022. In this article, I discuss and analyze the reproductive entanglements of surrogates, intended parents, and the children born through such transnational surrogacy arrangements in Ukraine and how this extreme crisis of war exposed and exacerbated existing vulnerabilities.

Reprowebs: a conceptual approach to elasticity and change in the global assisted reproduction industry.

In the last few decades, assisted reproductive technologies (ARTs) have become increasingly transregional and transnational, often involving travel within or between countries or even continents. Until recently, the global ART industry was marked by so-called 'reprohubs'-places (such as southern California, Dubai, Anand, and Mumbai) specializing in the provision of reproductive services. While reprohubs continue to exist, in the last few years, many have splayed out, transforming into something more akin to webs that encompass, but go beyond these hubs. These webs show a unique dynamic capability to tighten, entangle, or extend in reaction to local and global changes, a characteristic which became particularly obvious during the global Covid-19 pandemic. In this paper, we propose conceptualizing this new dynamic capability as 'reprowebs'-an approach that adds a new dimension to the existing conceptualization of reproductive travel and helps us to better understand current developments in the global ART industry.

Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity.

Posttranslational modification with SUMO is known to regulate the activity of transcription factors, but how SUMOylation of individual proteins might influence immunity is largely unexplored. The NFAT transcription factors play an essential role in antigen receptor-mediated gene regulation. SUMOylation of NFATc1 represses IL-2 in vitro, but its role in T cell-mediated immune responses in vivo is unclear. To this end, we generated a novel transgenic mouse in which SUMO modification of NFATc1 is prevented. Avoidance of NFATc1 SUMOylation ameliorated experimental autoimmune encephalomyelitis as well as graft-versus-host disease. Elevated IL-2 production in T cells promoted T reg expansion and suppressed autoreactive or alloreactive immune responses. Mechanistically, increased IL-2 secretion counteracted IL-17 and IFN-γ expression through STAT5 and Blimp-1 induction. Then, Blimp-1 repressed IL-2 itself, as well as the induced, proliferation-associated survival factor Bcl2A1. Collectively, these data demonstrate that prevention of NFATc1 SUMOylation fine-tunes T cell responses toward lasting tolerance. Thus, targeting NFATc1 SUMOylation presents a novel and promising strategy to treat T cell-mediated inflammatory diseases.

Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4.

The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4 abundance, suggesting an IRF1-IRF4-binding competition at the Il9 locus. Furthermore, IRF1 shapes Th9 cells with an interferon/Th1 gene signature. Consistently, IRF1 restricts the IL-9-dependent pathogenicity of Th9 cells in a mouse model of allergic asthma. Thus our study reveals that the molecular ratio between IRF4 and IRF1 balances Th9 fate, thus providing new possibilities for manipulation of Th9 differentiation.