COVID-19 abruptly halted scientific conferences and seminars in mid-March, forcing the scientific community to either postpone or adapt to a virtual format. We caught up with Carla V. Rothlin, Elina ...I. Zúñiga, Hongbo Chi, Rino Rappuoli, and Matthew Krummel to find out about the pros and cons of virtual conferences and seminars and how these could change the nature of scientific conferences. Carla (CVR) and Elina (EIZ) established Global ImmunoTalks in April this year; Hongbo (HC) helped organize the Immunometabolism Mini-Symposia series in May and June; Rino (RR) was one of the scientific organizers of the Transforming Vaccinology Keystone, which moved to a virtual format in June; and Matthew (MK) has been organizing Eco Seminars at the University of California, San Francisco since 2019.
A defining feature of resident gut macrophages is their high replenishment rate from blood monocytes attributed to tonic commensal stimulation of this site. In contrast, almost all other tissues ...contain locally maintained macrophage populations, which coexist with monocyte-replenished cells at homeostasis. In this study, we identified three transcriptionally distinct mouse gut macrophage subsets that segregate based on expression of Tim-4 and CD4. Challenging current understanding, Tim-4
CD4
gut macrophages were found to be locally maintained, while Tim-4
CD4
macrophages had a slow turnover from blood monocytes; indeed, Tim-4
CD4
macrophages were the only subset with the high monocyte-replenishment rate currently attributed to gut macrophages. Moreover, all macrophage subpopulations required live microbiota to sustain their numbers, not only those derived from blood monocytes. These findings oppose the prevailing paradigm that all macrophages in the adult mouse gut rapidly turn over from monocytes in a microbiome-dependent manner; instead, these findings supplant it with a model of ontogenetic diversity where locally maintained subsets coexist with rapidly replaced monocyte-derived populations.
Immune regulation by cytokines is crucial in maintaining immune homeostasis, promoting responses to infection, resolving inflammation, and promoting immunological memory. Additionally, cytokine ...responses drive pathology in immune-mediated disease. A crucial cytokine in the regulation of all aspects of an immune response is transforming growth factor beta (TGFβ). Although best known as a crucial regulator of T cell responses, TGFβ plays a vital role in regulating responses mediated by virtually every innate and adaptive immune cell, including dendritic cells, B cells, NK cells, innate lymphoid cells, and granulocytes. Here, we review our current knowledge of how TGFβ regulates the immune system, highlighting the multifunctional nature of TGFβ and how its function can change depending on location and context of action.
Monocytes are crucial immune cells involved in regulation of inflammation either directly or via differentiation into macrophages in tissues. However, many aspects of how their function is controlled ...in health and disease are not understood. Here we show that human blood monocytes activate high levels of the cytokine TGFβ, a pathway that is not evident in mouse monocytes. Human CD14
, but not CD16
, monocytes activate TGFβ via expression of the integrin αvβ8 and matrix metalloproteinase 14, which dampens their production of TNFα in response to LPS. Additionally, when monocytes differentiate into macrophages, integrin expression and TGFβ-activating ability are maintained in anti-inflammatory macrophages but down-regulated in pro-inflammatory macrophages. In the healthy human intestine, integrin αvβ8 is highly expressed on mature tissue macrophages, with these cells and their integrin expression being significantly reduced in active inflammatory bowel disease. Thus, our data suggest that integrin αvβ8-mediated TGFβ activation plays a key role in regulation of monocyte inflammatory responses and intestinal macrophage homeostasis.
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