OBJECTIVE Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that spread to the Caribbean in 2013 and the United States in 2014. CHIKV-infected patients develop inflammatory arthritis that can persist for months to years, but little is known about the rheumatologic and immunologic features of CHIKV arthritis in humans, particularly as compared to rheumatoid arthritis (RA). Here, we describe these features in a group of 10 American travelers who were nearly simultaneously infected while visiting Haiti in June 2014. METHODS Patients were assessed by history, physical examination, and laboratory studies. All patients with CHIKV arthritis had detectable anti-CHIKV IgG. Using cytometry by time of flight (CyTOF), we analyzed peripheral blood mononuclear cells in CHIKV-infected patients, healthy controls, and patients with untreated, active RA. RESULTS Among ten CHIKV-infected individuals, eight developed persistent symmetric polyarthritis, who otherwise met the 2010 ACR/EULAR criteria for (seronegative) RA. CyTOF analysis revealed that RA and CHIKV-infected patients had greater percentages of activated and effector CD4+ and CD8+ T cells than healthy controls. CONCLUSION In addition to similar clinical features, patients with CHIKV infection and RA develop highly similar peripheral T cell phenotypes. These overlapping clinical and immunologic features highlight a need for rheumatologists to consider CHIKV infection when evaluating patients with new, symmetric polyarthritis.

Most knowledge on NK cells are based on studies of what are now known as conventional NK (cNK) cells in the mouse spleen or human peripheral blood. However, recent studies in mice indicate the presence of tissue-resident NK (trNK) cells in certain organs, such as the liver, that display different markers and transcription factor dependencies as compared to cNK cells. Here we provide evidence from cytometry by time-of-flight analysis and humanized mice indicating that human CD49e-negative NK cells are tissue-resident in the liver. Thus, these studies indicate that trNK cells are evolutionarily conserved in humans and mice, providing a foundation to explore their role in human disease.

Background: Nrf2 has been implicated in regulating immune cell signaling and function.Results: Nrf2-deficient murine DCs exhibit enhanced maturation phenotype, increased ROS levels with dysregulation of antigen uptake capabilities, and altered intracellular signaling.Conclusion: Nrf2 regulates DC intracellular redox and immune function.Significance: Defining the role of Nrf2 in DC biology underpins development of potential Nrf2 targeted immunotherapeutics.

Background: HO-1 contributes to redox homeostasis and regulation of immature dendritic cell (DC) phenotype.Results: HO-1 inhibition results in increased ROS, activation of p38 MAPK-CREB/ATF1 pathway, and dysregulation of DC phenotype and function.Conclusion: HO-1 influences DC function through effects on p38 MAPK-CREB/ATF1 signaling pathway.Significance: This study provides new insights into the molecular pathways influenced by HO-1 in DCs.