Iglesias, M. | Search bioRxiv

bioRxiv2018

Type-I interferons inhibit interleukin-10 signaling and favor type 1 diabetes development in NOD mice

Destruction of insulin-producing {beta}-cells by autoreactive T lymphocytes leads to the development of type 1 diabetes. Type I interferons (TI-IFN) and interleukin-10 (IL-10) have been connected with the pathophysiology of this disease; however, their interplay in the modulation of diabetogenic T cells remains unknown. We have discovered that TI-IFN cause a selective inhibition of IL-10 signaling in effector and regulatory T cells, altering their responses. This correlates with diabetes development in NOD mice, where the inhibition is also spatially localized to T cells of pancreatic and mesenteric lymph nodes. IL-10 signaling inhibition is reversible and can be restored via blockade of TI-IFN/IFN-R interaction, paralleling with the resulting delay in diabetes onset and reduced severity. Overall, we propose a novel molecular link between TI-IFN and IL-10 signaling that helps better understand the complex dynamics of autoimmune diabetes development and reveals new strategies of intervention.\n\nAbbreviations

immunology↗

bioRxiv2017

Opponent assessment and conflict resolution through mutual motor coordination

Most animals fight by repeating complex stereotypic behaviors, yet the internal structure of these behaviors has rarely been dissected in detail. We characterized the internal structure of fighting behaviors by developing a machine learning pipeline that measures and classifies the behavior of individual unmarked animals on a sub-second timescale. This allowed us to quantify several previously hidden features of zebrafish fighting strategies. We found strong correlations between the velocity of the attacker and the defender indicating a dynamic matching of approach and avoidance efforts consistent with the cumulative assessment model of aggression. While velocity matching was ubiquitous, the spatial dynamics of attacks showed phase-specific differences. Contest phase attacks were characterized by a paradoxical side-ways attraction of the retreating animal towards the attacker suggesting that the defender combines avoidance maneuvers with display maneuvers. Post-resolution attacks lacked display-like features and the the defender was avoidance-focused. From the perspective of the winner, game theory modeling further suggested that highly energetically costly post resolution attacks occurred because the winner was trying to increase its relative dominance over the loser. Overall, the rich structure of zebrafish motor coordination during fighting indicates a greater complexity and layering of strategies than has previously been recognized.

animal behavior and cognition↗