Migratory DCs activate TGF-β to precondition naïve CD8 ⁺ T cells for tissue-resident memory fate

Abstract

Epithelial resident memory T (eTRM) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eTRM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8+ T cells and prepares them for the formation of eTRM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I–dependent interactions with peripheral tissue–derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β–activating αV integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.

Transforming Growth Factor-β: A Multifunctional Regulator of Cancer Immunity

“…Moreover, diverse cell types are involved in modulating the effects of TGF-β on the development and the reprogramming of the TME, as well as during cancer progression. For example, migratory dendritic cells (DCs) can activate TGF-β via an integrin-dependent manner and promote naïve CD8+ T cell differentiation into epithelial resident memory T cells (eTRM) [ 42 ]. Notably, the interactions between non-immune cells and immune cells are also essential for TGF-β activation and function.…”

“…These IL-10+IL-17+IFN-γ+ Tregs can confer immunotherapy resistance and poor survival in cancer patients [ 133 ]. Besides, DCs educate naïve CD8+ T cells for tissue-resident memory through secreting TGF-β1 [ 42 ]. DCs also suppress NK cell activities via TGF-β1, lymphotoxin alpha, IL-12 secretion, and STAT3 phosphorylation [ 134 ].…”

CD4+ Resident Memory T Cells Mediate Long-Term Local Skin Immune Memory of Contact Hypersensitivity in BALB/c Mice

“…CD4 + and CD8 + T RM cells are a subset of αβ T cell receptor (TCR) + memory T cells that fundamentally differ from their circulating counterparts and are characterized by their long-term residency within virtually all organs and unique transcriptional profiles (12)(13)(14)(15)(16). T RM cells differentiate within tissues from activated T cells (or T RM precursor cells), are maintained by local cytokine signals (17)(18)(19)(20)(21)(22), and thus are concentrated in previously infected or inflamed tissues. The major function of T RM cells is to provide protective immunity against pathogen re-entry into the same tissue; however, when generated in the context of allergy or autoimmune diseases, they are considered to cause disease relapse.…”

Cellular scars and local crosstalk in relapsing psoriasis: an example of a skin sticking disease

“…According to a recent study, skin DCs migrate to the lymph nodes, where they precondition naïve T cells to become 'future' memory T cells by producing TGF-β. 62 This priming step was fundamental for effective T cells establishment and persistence in the skin following cutaneous infections. In both human and mouse models, changes in skin homoeostasis lead to the infiltration of additional populations of DCs in the skin.…”