Modulation of CD4+ T Helper Cell Memory Responses in the Human Skin.

Immunological memory is defined as the capacity to mount faster and more effective immune responses against antigenic challenges that have been previously encountered by the host. CD4+ T helper (Th) cells play central roles in the establishment of immunological memory as they assist the functions of other leukocytes. Th cells express polarized cytokine profiles and distinct migratory and seeding capacities, but also retain a certain functional plasticity that allows them to modulate their proliferation, activity, and homing behaviour upon need. Thus, in healthy individuals, T cell immunomodulation fulfils the task of eliciting protective immune responses where they are needed. At times, however, Th plasticity can lead to collateral tissue damage and progression to autoimmune diseases or, conversely, incapacity to reject malignant tissues and clear chronic infections. Furthermore, common immune players and molecular pathways of diseases can lead to different outcomes in different individuals. A mechanistic understanding of those pathways is therefore crucial for developing precise and curative medical interventions. Here, I focus on the skin microenvironment and comprehensively describe some of the cellular and molecular determinants of CD4+ T cell memory responses in homeostatic and pathological conditions. In discussing the cellular network orchestrating cutaneous immunity, I comprehensively describe the bidirectional interaction of skin antigen-presenting cells and mononuclear phagocytes with Th17 lymphocytes, and examine how the outcome of this interaction is influenced by endogenous skin molecules, including sodium salts and neuropeptides.