Immunomodulation of salivary gland function due to cancer therapy.

Functional salivary glands (SG) are essential for maintaining oral health, and salivary dysfunction is a persistent major clinical challenge. Several cancer therapies also have off-target effects leading to SG dysfunction. Recent advances highlight the role of SG immune populations in homeostasis, dysfunction and gland regeneration. Here, we review what is known about SG immune populations during development and postnatal homeostasis. We summarize recent findings of immune cell involvement in SG dysfunction following cancer treatments such as irradiation (IR) for head and neck cancers, immune transplant leading to graft-versus-host-disease (GVHD) and immune checkpoint inhibitor (ICI) treatment. The role of immune cells in SG in both homeostasis and disease, is an emerging field of research that may provide important clues to organ dysfunction and lead to novel therapeutic targets.

Pernio and early SARS-CoV-2 variants: natural history of a prospective cohort and the role of interferon.

Cases of new-onset pernio and recurrences in our cohort align tightly with trends in mean 7-day COVID-19 positivity in Wisconsin and mean temperature in Madison, Wisconsin by month.

Pandemic-associated pernio harbors footprints of an abortive SARS-CoV-2 infection.

Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion.

Atto 465 Derivative Is a Nuclear Stain with Unique Excitation and Emission Spectra Useful for Multiplex Immunofluorescence Histochemistry.

Multiplex immunofluorescence (mIF) is an effective technique for the maximal visualization of multiple target proteins in situ. This powerful tool is mainly limited by the spectral overlap of the currently available synthetic fluorescent dyes. The fluorescence excitation wavelengths ranging between 405 and 488 nm are rarely used in mIF imaging and serve as a logical additional slot for a fluorescent probe. In the present study, we demonstrate that the addition of 2,3,4,5,6-pentafluoroaniline to Atto 465 NHS ester, creating Atto 465-pentafluoroaniline (Atto 465-p), generates a bright nuclear stain in the violet-blue region of the visible spectrum. This allows the 405 nm excitation and emission, classically used for nuclear counterstains, to be used for the detection of another target protein. This increases the flexibility of the mIF panel and, with appropriate staining and microscopy, enables the quantitative analysis of at least six targets in one tissue section. (J Histochem Cytochem XX: XXX-XXX, XXXX).