Environmental cues received during development shape dendritic cell responses later in life.

Environmental signals mediated via the aryl hydrocarbon receptor (AHR) shape the developing immune system and influence immune function. Developmental exposure to AHR binding chemicals causes persistent changes in CD4+ and CD8+ T cell responses later in life, including dampened clonal expansion and differentiation during influenza A virus (IAV) infection. Naïve T cells require activation by dendritic cells (DCs), and AHR ligands modulate the function of DCs from adult organisms. Yet, the consequences of developmental AHR activation by exogenous ligands on DCs later in life has not been examined. We report here that early life activation of AHR durably reduces the ability of DC to activate naïve IAV-specific CD8+ T cells; however, activation of naïve CD4+ T cells was not impaired. Also, DCs from developmentally exposed offspring migrated more poorly than DCs from control dams in both in vivo and ex vivo assessments of DC migration. Conditional knockout mice, which lack Ahr in CD11c lineage cells, suggest that dampened DC emigration is intrinsic to DCs. Yet, levels of chemokine receptor 7 (CCR7), a key regulator of DC trafficking, were generally unaffected. Gene expression analyses reveal changes in Lrp1, Itgam, and Fcgr1 expression, and point to alterations in genes that regulate DC migration and antigen processing and presentation as being among pathways disrupted by inappropriate AHR signaling during development. These studies establish that AHR activation during development causes long-lasting changes to DCs, and provide new information regarding how early life environmental cues shape immune function later in life.

Cardiac arrest/cardiopulmonary resuscitation increases anxiety-like behavior and decreases social interaction.

Advances in medical technology have increased the number of individuals who survive cardiac arrest/cardiopulmonary resuscitation (CPR). This increased incidence of survival has created a population of patients with behavioral and physiologic impairments. We used temperature manipulations to characterize the contribution of central nervous system damage to behavioral deficits elicited by 8 minutes of cardiac arrest/CPR in a mouse model. Once sensorimotor deficits were resolved, we examined anxiety-like behavior with the elevated plus maze and social interaction with an ovariectomized female. We hypothesized that anxiety-like behavior would increase and social interaction would decrease in mice subjected to cardiac arrest/CPR and that these changes would be attributable to central nervous system damage rather than damage to peripheral organs or changes orchestrated by the administration of epinephrine. Mice that were subjected to cardiac arrest/CPR while the peripheral organs, but not the brain, were protected by hypothermia exhibited increased anxiety-like behavior and decreased social interaction, whereas mice with hypothermic brains and peripheral organs during cardiac arrest/CPR did not exhibit behavioral impairments. The present study demonstrates that central nervous system damage from cardiac arrest/CPR results in increased anxiety and decreased social interaction and that these behavioral changes are not attributed to underlying sensorimotor deficits, dynamics of arrest and CPR, or peripheral organ damage.