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 in the liver 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 of major tissue systems; in the thymus, for instance, and also the peripheral nervous system. 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 cells throughout the body, making a primary signal origin for T and B cells in a great diversity of inflammatory, reparative, and clearance processes. 2MP1 is also documented within the marginal tissues between large intestine and the appendix, called the cecum. (Swiss Institute of Bioinformatics (SIB), 2022) Chemokine Ligand #19 also has a degree of prominence in neural tissues, having been identified in both the cranial nerve tract (Cranial Nerve II) and the optic nerve itself (in less-cogent form), functioning as one element in the responsive transfer medium of optical data between the retina and the brain. (Swiss Institute of Bioinformatics (SIB), 2022).

Further, 2MP1 expression is suffusive beneath the dermal layer, secreted by follicular fibroblasts, directing replicative skin repair. (Topouzi & Higgins, 2020) 2MP1 fulfills a similar function in the respiratory system, where it is intimately involved in Bronchus Associated Lymphoid [clearance] Tissues (iBALT). (Swiss Institute of Bioinformatics (SIB), 2022)

In fact, 2MP1 is also the indispensable secretory element of Follicle Associated Epithelium (FAE) cells in mucosal tissues in 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) As such, C-C motif Ligand #19 (CCL19, hereafter) is 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 prominence in virion-clearance tissues in the major organ systems (gastrointestinal and respiratory). Most recently, the CCR7-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 antigens (DCs) on the surface developed by the complex; (Wenxiang Hong, 2022) ultimately transferred to the primary T-Cells the CCL19:CCR7 complex activates. Innate leukocytes are more readily activated than adaptive leukocytes because adaptive leukocytes are not already part of the thymic memory, stored in the lymph nodes.

These identified functions of CCL19 exemplify the signaling activities unique to this pivotal ligand. 2MP1 is expressed most prominently in the thymus and in the lymphatic/lymphoid organs, and less prominently in the small intestine. (ELIXIR Core Data Resources, 2022) With its receptor CCR7, 2MP1 is essential in modulation, activation, and re/circulation of T and B lymphocytes, granulocytes, and all leukocyte forms between the lymphoid organs and between layers of tissue.

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