Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction

International audienceThe PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals

Perceived inequity, professional and personal fulfillment by women intensivists in France

International audienceBackground: The medical workforce has been feminized for the last two decades worldwide. Nonetheless, women remain under-represented among intensivists. We conducted a survey among French women intensivists to assess their professional and personal quality of life and their perception of potential gender discrimination at work.Methods: We conducted an observational descriptive study by sending a survey, designed by the group FEMMIR (FEmmes Médecins en Médecine Intensive Réanimation), to women intensivists in France, using primarily the Société de Réanimation de Langue Française (SRLF) mailing list. The questionnaire was also available online between September 2019 and January 2020 and women intensivists were encouraged to answer through email reminders. It pertained to five main domains, including demographic characteristics, work position, workload and clinical/research activities, self-fulfillment scale, perceived discrimination at work and suggested measures to implement.Results: Three hundred and seventy-one women responded to the questionnaire, among whom 16% had an academic position. Being a woman intensivist and pregnancy were both considered to increase difficulties in careers’ advancement by 31% and 73% of the respondents, respectively. Almost half of the respondents (46%) quoted their quality of life equal to or lower than 6 on a scale varying from 1 (very bad quality of life) to 10 (excellent quality of life). They were 52% to feel an imbalance between their personal and professional life at the cost of their personal life. Gender discrimination has been experienced by 55% of the respondents while 37% confided having already been subject of bullying or harassment. Opportunities to adjust their work timetable including part-time work, better considerations for pregnant women including increasing the number of intensivists and the systematic replacement during maternity leave, and the respect of the law regarding the paternity leave were suggested as key measures to enable better professional and personal accomplishment by women intensivists.Conclusion: In this first large French survey in women intensivists, we pointed out issues felt by women intensivists that included an imbalance between professional and personal life, a perceived loss of opportunity due to the fact of being a woman, frequent reported bullying or harassment and a lack of consideration of the needs related to pregnancy and motherhood