Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy

Abstract

Owners and their domestic animals via skin shedding and secretions, mutually exchange microbiomes, potential pathogens and innate immune molecules. Among the latter especially lipocalins are multifaceted: they may have an immunomodulatory function and, furthermore, they represent one of the most important animal allergen families. The amino acid identities, as well as their structures by superposition modeling were compared among human lipocalins, hLCN1 and hLCN2, and most important animal lipocalin allergens, such as Can f 1, Can f 2 and Can f 4 from dog, Fel d 4 from cats, Bos d 5 from cow's milk, Equ c 1 from horses, and Mus m 1 from mice, all of them representing major allergens. The β‐barrel fold with a central molecular pocket is similar among human and animal lipocalins. Thereby, lipocalins are able to transport a variety of biological ligands in their highly conserved calyx‐like cavity, among them siderophores with the strongest known capability to complex iron (Fe3+). Levels of human lipocalins are elevated in nonallergic inflammation and cancer, associated with innate immunoregulatory functions that critically depend on ligand load. Accordingly, deficient loading of lipocalin allergens establishes their capacity to induce Th2 hypersensitivity. Our similarity analysis of human and mammalian lipocalins highlights their function in innate immunity and allergy.

Changes in salivary analytes in canine parvovirus: A high-resolution quantitative proteomic study

“…On the other hand, the two most up-regulated proteins in dogs with parvovirosis that survived, were lipocalin-9 (LCN9) and BPI fold-containing family B member 2 (BPiFB2). Lipocalins are a family of proteins that usually carry lipids or other hydrophobic or amphiphilic compounds accommodated in a cavity within their conformation, including steroids, hormones and metabolites such as vitamins and cofactors [44]. Furthermore, lipocalins have been reported to be modulators of cell growth and metabolism, and regulators of the immune response [45,46].…”

Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans

“…in COPD (chronic obstructive pulmonary disease) [35] and cystic fibrosis [36]. Animal lipocalins are known allergens promoting Th2 responses and inflammation [37]. Thus, it is probable that LCN1 may also contribute to allergen-mediated Th2-skewed inflammation following inhaled DE exposure.…”

AllergoOncology: Microbiota in allergy and cancer—A European Academy for Allergy and Clinical Immunology position paper

“…In line with the hygiene hypothesis, the limited “microbial exposure” of allergic individuals may also result in deficiencies of the immune regulatory machinery and this can lead to hyper‐reactive responses . Interestingly, nearly all major mammalian allergens belong to the lipocalin family, and are similarly able to bind to bacterial and plant‐derived iron chelators, pointing to a potential role for interference of LCN2 function. In several cancer types and in line with a perturbed iron regulation, LCN2 plays an important role in oncogenesis and cancer progression and may serve as a disease biomarker …”