The Central Roles of Keratinocytes in Coordinating Skin Immunity.

The function of keratinocytes (KCs) to form a barrier and produce cytokines is well-known, but recent progress has revealed many different roles for KCs in regulation of skin immunity. In this review, we provide an update on the current understanding of how KCs communicate with microbes, immunocytes, neurons, and other cells to form an effective immune barrier. We catalog the large list of genes and metabolites of KCs that participate in host defense and discuss the mechanisms of immune crosstalk, addressing how KCs simultaneously form a physical barrier, communicate with fibroblasts, and control immune signals. Overall, the signals sent and received by KCs are an exciting group of therapeutic targets to explore in the treatment of dermatologic disorders.

Multimodal Mass Spectrometry Imaging of Rat Brain Using IR-MALDESI and NanoPOTS-LC-MS/MS.

Multimodal mass spectrometry imaging (MSI) is a critical technique used for deeply investigating biological systems by combining multiple MSI platforms in order to gain the maximum molecular information about a sample that would otherwise be limited by a single analytical technique. The aim of this work was to create a multimodal MSI approach that measures metabolomic and proteomic data from a single biological organ by combining infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) for metabolomic MSI and nanodroplet processing in one pot for trace samples (nanoPOTS) LC-MS/MS for spatially resolved proteome profiling. Adjacent tissue sections of rat brain were analyzed by each platform, and each data set was individually analyzed using previously optimized workflows. IR-MALDESI data sets were annotated by accurate mass and spectral accuracy using HMDB, METLIN, and LipidMaps databases, while nanoPOTS-LC-MS/MS data sets were searched against the rat proteome using the Sequest HT algorithm and filtered with a 1% FDR. The combined data revealed complementary molecular profiles distinguishing the corpus callosum against other sampled regions of the brain. A multiomic pathway integration showed a strong correlation between the two data sets when comparing average abundances of metabolites and corresponding enzymes in each brain region. This work demonstrates the first steps in the creation of a multimodal MSI technique that combines two highly sensitive and complementary imaging platforms. Raw data files are available in METASPACE (https://metaspace2020.eu/project/pace-2021) and MassIVE (identifier: MSV000088211).