Zimmerli Simone C, Hauser Conrad
Allergy Unit, Division of Immunology and Allergy, Department of Internal Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland.
J Invest Dermatol. 2007 Oct;127(10):2381-90. doi: 10.1038/sj.jid.5700882. Epub 2007 May 17.
Claudin-1 is a critical structural component of tight junctions that have an important role in adhesive properties, barrier function, and paracellular transport of epithelia and other nonhematopoietic tissues. We found claudin-1 in murine CD207+ Langerhans cells (LC) residing in epidermis. Claudin-1 was not detected in other skin dendritic cells (DC). LC expressed claudin-1 in steady state and inflamed skin. Claudin-1 was demonstrated further in lymph node LC under steady state and inflammatory conditions, including after direct tracking with tetramethylrhodamine-isothiocyanate (TRITC). All subsets of skin draining lymph node DC defined by CD205, CD11b, CD11c, and CD8, including a presumably blood-borne lymph node resident CD8+CD207+ LC population, were claudin-1+. TRITC tracking demonstrated claudin-1 in CD207- skin migrant DC in the lymph node, suggesting upregulation of this molecule during migration or once arrived in the lymph node. Claudin-1 expression in CD207+ cells was confirmed at the protein and mRNA levels. Transforming growth factor-beta, a factor critical for the induction of LC in vitro and in vivo, stimulated the accumulation of claudin-1 mRNA and protein when added to bone marrow cells cultured with GM-CSF and IL-4. Claudin-1 may thus have an important function in adhesion and/or migration of LC.
Claudin-1是紧密连接的关键结构成分,紧密连接在上皮细胞和其他非造血组织的黏附特性、屏障功能及细胞旁转运中起重要作用。我们在位于表皮的小鼠CD207⁺朗格汉斯细胞(LC)中发现了Claudin-1。在其他皮肤树突状细胞(DC)中未检测到Claudin-1。LC在稳态和炎症皮肤中均表达Claudin-1。在稳态和炎症条件下,包括用异硫氰酸四甲基罗丹明(TRITC)直接追踪后,在淋巴结LC中进一步证实了Claudin-1的存在。由CD205、CD11b、CD11c和CD8定义的引流皮肤的淋巴结DC的所有亚群,包括可能源自血液的驻留淋巴结的CD8⁺CD207⁺LC群体,均为Claudin-1阳性。TRITC追踪显示淋巴结中CD207⁻皮肤迁移DC中有Claudin-1,提示该分子在迁移过程中或一旦到达淋巴结后会上调。在蛋白质和mRNA水平上均证实了CD207⁺细胞中Claudin-1的表达。转化生长因子-β是体内外诱导LC的关键因子,当添加到用GM-CSF和IL-4培养的骨髓细胞中时,可刺激Claudin-1 mRNA和蛋白质的积累。因此,Claudin-1可能在LC的黏附和/或迁移中起重要作用。