PD-1 is requisite for skin T_RM cell formation and specification by TGFβ

Area of Science:

• Immunology
• Cell Biology
• Dermatology

Background:

• Tissue-resident memory T (T_RM) cells are vital for immunity at barrier sites, including skin, and play roles in cancer and autoimmunity.
• Immune checkpoint proteins, such as programmed death receptor 1 (PD-1), are involved in regulating T cell responses and are targets for cancer immunotherapy.
• The specific role of PD-1 in the initial development and programming of skin T_RM cells remains incompletely understood.

Purpose of the Study:

• To investigate the impact of programmed death receptor 1 (PD-1) signaling on the early specification and programming of CD8⁺ T_RM cells in the skin.
• To determine if PD-1 expression is maintained on skin T_RM cells under various conditions, including aging.

Main Methods:

• Analysis of PD-1 expression on mouse and human skin T_RM cells.
• Investigating the effects of PD-1 signaling on T_RM cell colonization, differentiation, and TGFβ responsiveness in skin models.
• Studying PD-1 expression on skin T_RM cells in aged mice.

Main Results:

• PD-1 is broadly expressed on skin T_RM cells, independent of persistent infection, and is retained in aged mice.
• PD-1 signaling was found to be essential for early T_RM cell colonization of the skin.
• PD-1 promotes skin-specific programming, silences alternative differentiation pathways, and enhances TGFβ responsiveness and skin engraftment.

Conclusions:

• PD-1 signaling is a critical mediator of skin T_RM cell specification during the initiation of immune responses.
• These findings highlight the role of PD-1 in establishing protective memory in the skin.
• Understanding PD-1's function in T_RM cell development may guide the therapeutic use of PD-1 agonists and antagonists for modulating peripheral immune memory.