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<p>Dermal resident memory CD4<sup>+</sup> 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 <i>Leishmania</i>-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 <i>Leishmania</i>. These findings highlight IL-12 as a key driver of CD4<sup>+</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月16日

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  • Anabel Zabala-Peñafiel,
  • Claudia Gonzalez-Lombana,
  • Mohamad-Gabriel Alameh,
  • Lais A. Sacramento,
  • Zhirong Mou,
  • Anthony T. Phan,
  • Emily A. Aunins,
  • Ying K. Tam,
  • Jude E. Uzonna,
  • Drew Weissman,
  • Christopher A. Hunter,
  • Phillip Scott

摘要

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.