Tissue-resident memory T (TRM) cells exist throughout the body, where they are poised to mediate local immune responses. Although studies have defined a common mechanism of residency independent of location, there is likely to be a level of specialization that adapts TRM cells to their given tissue of lodgment. It has been shown that TRM cells in the skin rely on the uptake of exogenous fatty acids for their survival and up-regulate fatty acid–binding protein 4 (FABP4) and FABP5 as part of their transcriptional program. However, FABPs exist as a larger family of isoforms, with different members selected in a tissue-specific fashion that is optimized for local fatty acid availability. Here, we show that although TRM cells in a range of tissue widely express FABPs, they are not restricted to FABP4 and FABP5. Instead, TRM cells show varying patterns of isoform usage that are determined by tissue-derived factors. These patterns are malleable because TRM cells relocated to different organs modify their FABP expression in line with their new location. As a consequence, these results argue for tissue-specific overlays to the TRM cell residency program, including FABP expression that is tailored to the particular tissue of TRM cell lodgment.

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Biologics are the most rapidly growing class of therapeutics, but commonly suffer from low stability. Peroral administration of these therapeutics is an attractive delivery route; however, this route introduces unique physiological challenges that increase the susceptibility of proteins to lose function. Formulation of proteins into biomaterials, such as electrospun fibers, is one strategy to overcome these barriers, but such platforms need to be optimized to ensure protein stability and maintenance of bioactivity during the formulation process. This work develops an emulsion electrospinning method to load proteins into Eudragit® L100 fibers for peroral delivery. Horseradish peroxidase and alkaline phosphatase are encapsulated with high efficiency into fibers and released with pH-specificity. Recovery of protein bioactivity is enhanced through reduction of the emulsion aqueous phase and the inclusion of a hydrophilic polymer excipient. Finally, we show that formulation of proteins in lyophilized electrospun fibers extends the therapeutic shelf life compared to aqueous storage. Thus, this platform shows promise as a novel dosage form for the peroral delivery of biotherapeutics.

Oral vaccines have the potential to reduce cost, improve compliance, and induce immunity at mucosal surfaces that are the first line of defense against infection. The gastrointestinal tract is highly evolved to efficiently digest and absorb nutrients without eliciting aberrant inflammation. However, these functions also limit the efficacy of immunization by the oral route. While mechanisms responsible for the development of tolerance to fed antigens are being illuminated, the application of materials with precise physiochemical properties and immunomodulatory potential may accelerate understanding of immunity within the gastrointestinal tract. Insight into these immunological mechanisms can inform the design of next‐generation oral vaccines to harness critical functions to elicit immunity. Here, material strategies for oral vaccines and their dual function in understanding and overcoming immunological barriers associated with oral immunization are discussed.