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Updated: Sep 15, 2025
Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
IL-12 mRNA-LNP promotes dermal resident memory CD4+ T cell development
Anabel Zabala-Peñafiel1, Claudia Gonzalez-Lombana1, Mohamad-Gabriel Alameh2
1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
Dermal resident memory CD4+ T cells (dTrm) provide protection 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.
Insights
Interleukin-12 (IL-12) mRNA combined with a vaccine enhances CD4+ T cells in the skin (dTrm). This improves immunity against leishmaniasis and other skin infections.
Area of Science:
- Immunology
- Vaccinology
- Infectious Diseases
Background:
- Dermal resident memory CD4+ T cells (dTrm) are crucial for protection against skin infections.
- Factors influencing dTrm cell development are not fully understood.
- mRNA vaccines show potential but require optimization for skin immunity.
Purpose of the Study:
- To investigate if mRNA vaccination can induce dTrm cells.
- To determine if combining IL-12 mRNA with a vaccine enhances dTrm development.
- To assess the functional immunity conferred by IL-12-enhanced vaccination.
Main Methods:
- mRNA vaccine encoding a leishmanial antigen was administered to mice.
- IL-12 mRNA was co-administered with the vaccine in a separate group.
- T cell populations, skin-homing markers, and memory markers were analyzed.
- Delayed hypersensitivity responses and protection against Leishmania challenge were assessed.
Main Results:
- Single mRNA vaccination induced systemic T cell responses but limited skin Trm cells.
- IL-12 mRNA combined with the vaccine expanded Leishmania-specific Th1 cells in lymph nodes.
- Enhanced vaccine strategy increased dTrm cell numbers in the skin.
- Mice receiving the combination vaccine showed improved functional immunity and protection.
Conclusions:
- IL-12 is a critical factor in promoting CD4+ dTrm cell development and skin seeding.
- IL-12-enhanced mRNA vaccines can generate durable immunity against cutaneous leishmaniasis.
- This approach holds promise for developing vaccines against other skin-targeted infections.
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