Characteristics and sources of tissue-resident memory T cells in psoriasis relapse

Abstract

Tissue-resident memory T cells (Trm) are a sub-population of memory T cells that reside in skin tissue. Recent studies have revealed potential role of Trm in the reoccurrence of psoriasis, as these cells tend to be profusely infiltrated in the lesions observed during psoriasis relapse. Trm can be classified into CD8⁺ Trm cells that are distributed mainly in the epidermis and CD4⁺ Trm cells in the dermis. CD8⁺ Trm is derived from circulating memory T cells and CD49a^-CD8⁺ Trm takes a crucial role in psoriasis relapse. In contrast, CD4⁺ Trm may originate from exTh17 cells and exTreg cells emerging from the inflammatory process. Since IL-23 can activate Trm, neutralizing antibodies against IL-23 are suggested to be more effective in clinical treatment. This review will focus on Trm cells in psoriasis relapsed lesions to reveal their mechanisms in the pathogenesis, relapse and transformation of psoriasis.

Keywords: Psoriasis; Relapse; Th17; Trm.

Graphical abstract

Fig. 1

(1) Surface markers of Trm: Integral proteins (CD69, CD103, CD49a), which are primarily responsible for the tissue residence of Trm. Chemokine receptors (CXCR3, CXCR6, CCR4, CCR10), capable of driving precursor memory cells into the skin. Costimulatory molecules (CD28, etc.) responsible for maintaining the stability of T cells. (2) Source of CD8⁺Trm:Circulating CD8⁺ T cells are able to differentiate into SLEC and MPEC. SLEC apoptosis after the inflammation subsides and MPEC continue to differentiate. One of the memory precursor cells with the phenotype KLRG1^-CD127⁺CD45RO⁺CD45RA^- eventually differentiates into CD8⁺Trm.SLEC: short-lived effector cells; MPEC: memory precursor effector cells.

Fig. 2

Self-proliferation in the presence of IL-7, IL-15, TGF-β and lipid. (ii) Activation phase: Trm is activated in response to stimulation by IL-23 secreted by DCs. (iii)Onset stage: CD49a⁻CD8⁺Trm secretion of IL-17 is involved in psoriasis relapse. IFN-γ secreted by CD49a⁻CD8⁺ Trm acts on DCs to form an inflammatory cycle while activating KC. IL-22 secreted by CD4⁺ Trm recruits inflammatory cells into the superficial dermis to participate in psoriasis relapse.