School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 1UL, UK.
Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK.
Protein Cell. 2022 Jul 15;14(1):4-16. doi: 10.1093/procel/pwac012. eCollection 2023 Jan.
C-type lectins (CTLs) represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains (CRDs) to glycan residues presented on the surface of a variety of pathogens. The deconvolution of a cell's glycan code by CTLs underpins several important physiological processes in mammals such as pathogen neutralization and opsonization, leukocyte trafficking, and the inflammatory response. However, as our knowledge of CTLs has developed it has become apparent that the role of this innate immune family of proteins can be double-edged, where some pathogens have developed approaches to subvert and exploit CTL interactions to promote infection and sustain the pathological state. Equally, CTL interactions with host glycoproteins can contribute to inflammatory diseases such as arthritis and cancer whereby, in certain contexts, they exacerbate inflammation and drive malignant progression. This review discusses the 'dual agent' roles of some of the major mammalian CTLs in both resolving and promoting infection, inflammation and inflammatory disease and highlights opportunities and emerging approaches for their therapeutic modulation.
C 型凝集素(CTLs)是一大类可溶性和膜结合蛋白家族,通过碳水化合物识别结构域(CRDs)与各种病原体表面呈现的糖基残基结合,从而依赖钙结合。CTLs 通过对细胞糖码的剖析,为哺乳动物的几个重要生理过程提供了支持,如病原体中和和调理作用、白细胞迁移和炎症反应。然而,随着我们对 CTLs 的认识不断发展,人们已经意识到这个先天免疫蛋白家族的作用可能是一把双刃剑,一些病原体已经开发出一些方法来颠覆和利用 CTL 相互作用,以促进感染并维持病理状态。同样,CTL 与宿主糖蛋白的相互作用也可能导致关节炎和癌症等炎症性疾病,在某些情况下,它们会加剧炎症并推动恶性进展。这篇综述讨论了一些主要哺乳动物 CTLs 在解决和促进感染、炎症和炎症性疾病方面的“双重作用”,并强调了对其治疗调节的机会和新兴方法。