Data from: IL-12 mRNA-LNP promotes dermal resident memory CD4+ T cell development

Dermal resident memory CD4+ T cells (dTrm) protect against vector-borne
infections. However, the factors that promote their development remain
unclear. We tested if an mRNA vaccine, encoding a protective leishmanial
antigen, induced dTrm cells. The mRNA vaccine induced robust systemic
T-cell responses, but few Trm cells were found in the skin. Since IL-12
promotes Th1 responses, we tested whether IL-12 mRNA combined with the
mRNA vaccine could enhance dTrm cell development. This combination
significantly expanded Leishmania-specific Th1 cells expressing
skin-homing molecules and memory T cell markers in the draining lymph
node. Additionally, higher numbers of dTrm cells were maintained in the
skin, and mice exhibited functional immunity, indicated by a delayed
hypersensitivity response and protection upon challenge with Leishmania.
These findings highlight IL-12 as a key driver of CD4+ dTrm development,
enabling their global seeding across the skin, and underscore the
potential of IL-12-enhanced mRNA vaccines to generate durable immunity
against cutaneous leishmaniasis and other skin-targeted infections.