Description

Name: Jeffrey Eldrige | [ from ] "CCL19 Expression Quantification Assay" Chemokine Ligand 19 is designated “2MP1” by the Worldwide Protein Data Bank. 2MP1 (commonly CCL19) is a signaling protein, key to immunological responses of lymphoid and thymic tissues. Chemokine Ligand #19 is also key to a broad class of (both) acute and chronic inflammatory processes (Gowhari Shabgah A, 2022), especially those involving lymphatic and gastrointestinal systems. Consequently, 2MP1 is associated with chronic human illnesses (including psoriasis and cancers), especially due to its involvement with immunological responses in lymphoid and vascular tissues. The nomenclature surrounding the so-called “C-C motif” proteins (CCL19 being one) is a reference to the arrangement of their amino acid backbones, all of which have a pair of cysteine residues at their centers. Cysteine-Cysteine disulfide bridge formation is fundamental to molecular infrastructure, across the human proteome. (Wiedemann, et al., 2020) This makes the “C-C motif” proteins a particularly well-stabilized subfamily of Cytokines. The chemokine family of biomolecules are chemotactic cytokines, meaning these are plenipotentiary secretions of immune cells; modulating, activating, and transporting immune responses. Cytokines are the surveilling praxis of chemical-induced signaling in all lymphoid organs, especially in synthesis and transport of T-Cells. Found most frequently in filament regions between related but separable organs, chemokines are dispersed throughout the layers and epithelial networks of major tissue systems; in the thymus, for instance, and also the central and peripheral nervous systems. (ELIXIR Core Data Resources, 2022) Cytokines bind to the surface of specific receptors imbedded in such connective regions, in order to secrete signals that direct subsequent transcription in processes downstream. Human protein 2MP1 is present in epithelial networks throughout the body, making it a primary signal origin for T and B cells in a great diversity of inflammatory, reparative, and clearance processes. 2MP1 is also highly expressed in Peyer’s Patches, (Swiss Institute of Bioinformatics (SIB), 2022) the branching surveillance nodes dispersed throughout the ileum, at the base of the small intestine. Between its high endotheleal expression and its prominence in the appendix, 2MP1 brackets the large intestine and the cecum (Swiss Institute of Bioinformatics (SIB), 2022); the cecum being a marginal structure that transports expelled salts and other waste out of the ileum. But CCL19’s modulatory importance may be further elucidated by the fact that the ileum is the primary source of B12 for neurological systems, in humans. (Bielecki B, 2015) Not surprisingly, Chemokine Ligand #19 has a moderately-high degree of expression in neural tissues; especially the Central Nervous System (CNS), having been identified in both the cranial nerve tract (Cranial Nerve II) (Swiss Institute of Bioinformatics (SIB), 2022) and in the optic nerve itself (Wang T, 2021). 2MP1 is also prominent in the retina’s pigmentation layer (Swiss Institute of Bioinformatics (SIB), 2022), functioning as one element in the responsive transfer medium of optical data between the retina and the brain. Further, 2MP1 expression is suffusive beneath the dermal layer, secreted (in particular) by follicular fibroblasts, directing replicative skin repair. (Topouzi & Higgins, 2020) 2MP1 fulfills a similar function in the respiratory system, (Rangel-Moreno, 2007) where it is intimately involved in Bronchus Associated Lymphoid [clearance] Tissues (iBALT). (Hwang, 2016) 2MP1 is also the indispensable secretory element of Follicle Associated Epithelium (FAE) cells in mucosal tissues throughout the gastrointestinal organs. (Noah P. Zimmerman, 2008) Recent research suggests mucosal surfaces of intestinal lymph nodes may be the primary source of the immune system in humans. (Smith, 2006) This hypothesis, along with this ligand’s aforementioned prominence for neurotaxis in the CNS indicates C-C motif Ligand #19 (CCL19, hereafter) as a key target in the emerging field of Neuro-Immune Physiology. (Yan, 2021) CCL19 is the internalization ligand of its receptor, CCR7, (Haessler, 2011) with a strong affinity towards desensitization mechanisms in immune responses. This proficiency in affecting internalization (inside damaged tissues), unique to CCL19, is highly-attenuated; providing a viable explanation for CCR7’s importance in virion-clearance tissues in the major organ systems (gastrointestinal and respiratory). Most recently, the CCR7:CCL19 axis has been shown to be the major inductive signal leading to iBALT formation. (Nancy D. Marin, 2019) A core function for CCL19 is modulation between innate and adaptive leukocyte function, (Yan, 2021) a process affected by the protein’s complexing with dendritic cells (DCs) specific to given immunological conditions. CCL19 stimulation induces presentation of these CCR7-bearing