The C-C chemokine receptor 7: An immune molecule that modulates central nervous system function in homeostasis and disease.

The interaction between the central nervous system (CNS) and the peripheral immune system is key for brain function in homeostasis and disease. Recent studies have revealed that the C-C chemokine receptor 7 (CCR7) is expressed in both CNS resident cells and peripheral immune cells, and plays an important role in regulating behavior in homeostasis and neuroinflammation in disease. This review integrates studies examining the role of CCR7 in CNS resident and peripheral immune cells in homeostasis and disease, as well as the pathways of peripheral immune cell migration in and out of the brain via CCR7. A special emphasis is placed on the CCR7-dependent migration of peripheral immune cells into the recently discovered meningeal lymphatic vessels surrounding the brain and nasal lymphatics, its migration into cervical lymph nodes, and the implications that this migration might have for CNS function.

Selective integration of diverse taste inputs within a single taste modality.

A fundamental question in sensory processing is how different channels of sensory input are processed to regulate behavior. Different input channels may converge onto common downstream pathways to drive the same behaviors, or they may activate separate pathways to regulate distinct behaviors. We investigated this question in the Drosophila bitter taste system, which contains diverse bitter-sensing cells residing in different taste organs. First, we optogenetically activated subsets of bitter neurons within each organ. These subsets elicited broad and highly overlapping behavioral effects, suggesting that they converge onto common downstream pathways, but we also observed behavioral differences that argue for biased convergence. Consistent with these results, transsynaptic tracing revealed that bitter neurons in different organs connect to overlapping downstream pathways with biased connectivity. We investigated taste processing in one type of downstream bitter neuron that projects to the higher brain. These neurons integrate input from multiple organs and regulate specific taste-related behaviors. We then traced downstream circuits, providing the first glimpse into taste processing in the higher brain. Together, these results reveal that different bitter inputs are selectively integrated early in the circuit, enabling the pooling of information, while the circuit then diverges into multiple pathways that may have different roles.

Biobehavioral Implications of Covid-19 for Transplantation and Cellular Therapy Recipients.

A growing body of literature has emphasized the importance of biobehavioral processes - defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes - for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19.