Patra VijayKumar, Strobl Johanna, Atzmüller Denise, Reininger Bärbel, Kleissl Lisa, Gruber-Wackernagel Alexandra, Nicolas Jean-Francois, Stary Georg, Vocanson Marc, Wolf Peter
Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale, U1111, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, UMR 5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France.
Research Unit for Photodermatology, Medical University of Graz, Graz, Austria.
Front Med (Lausanne). 2022 Jun 10;9:908047. doi: 10.3389/fmed.2022.908047. eCollection 2022.
Patients with polymorphic light eruption (PLE) develop lesions upon the first exposure to sun in spring/summer, but lesions usually subside during season due to the natural (or medical) photohardening. However, these lesions tend to reappear the following year and continue to do so in most patients, suggesting the presence of a disease memory. To study the potential role of skin resident memory T cells (Trm), we investigated the functional phenotype of Trm and the expression of IL-15 in PLE. IL-15 is known to drive Trm proliferation and survival. Multiplex immunofluorescence was used to quantify the expression of CD3, CD4, CD8, CD69, CD103, CD49a, CD11b, CD11c, CD68, granzyme B (GzmB), interferon-gamma (IFN-γ), and IL-15 in formalin-fixed, paraffin-embedded lesional skin samples from PLE patients and healthy skin from control subjects. Unlike the constitutive T cell population in healthy skin, a massive infiltration of T cells in the dermis and epidermis was observed in PLE, and the majority of these belonged to CD8 T cells which express Trm markers (CD69, CD103, CD49a) and produced cytotoxic effector molecules GzmB and IFN-γ. Higher numbers of CD3 T cells and CD11bCD68 macrophages produced IL-15 in the dermis as compared to healthy skin. The dominant accumulation of cytotoxic Trm cells and increased expression of IL-15 in lesional skin of PLE patients strongly indicates the potential role of skin Trm cells in the disease manifestation and recurrence.
多形性日光疹（PLE）患者在春夏季首次暴露于阳光下时会出现皮损，但由于自然（或医学）光硬化作用，皮损通常在季节内消退。然而，这些皮损往往在次年再次出现，并且大多数患者会持续如此，这表明存在疾病记忆。为了研究皮肤驻留记忆T细胞（Trm）的潜在作用，我们调查了Trm的功能表型以及PLE中IL-15的表达。已知IL-15可驱动Trm的增殖和存活。采用多重免疫荧光法对PLE患者福尔马林固定、石蜡包埋的皮损样本以及对照受试者的健康皮肤中CD3、CD4、CD8、CD69、CD103、CD49a、CD11b、CD11c、CD68、颗粒酶B（GzmB）、干扰素-γ（IFN-γ）和IL-15的表达进行定量。与健康皮肤中的组成性T细胞群体不同，在PLE中观察到真皮和表皮中有大量T细胞浸润，其中大多数属于表达Trm标志物（CD69、CD103、CD49a）并产生细胞毒性效应分子GzmB和IFN-γ的CD8 T细胞。与健康皮肤相比，真皮中产生IL-15的CD3 T细胞和CD11bCD68巨噬细胞数量更多。PLE患者皮损皮肤中细胞毒性Trm细胞的显著积累以及IL-15表达的增加强烈表明皮肤Trm细胞在疾病表现和复发中具有潜在作用。
