Blockade of RANKL/RANK interaction prevents allergic airway inflammation in a mouse model of asthma

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 65 - 65.21
• Main Authors: Maslanka, Tomasz, Gregorczyk, Izabela, Jasiecka-Mikolajczyk, Agnieszka
• Format: Journal Article
• Language: English
• Published: 01-05-2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.65.21

W are constantly looking for new therapeutic options for asthma treatment. In this study, we investigated whether the signaling pathway of the receptor activator of nuclear factor (NF)-κB (RANK), RANK ligand (RANKL), and its decoy receptor osteoprotegerin (OPG) may be considered as a novel drug target for therapy of allergic asthma. Therefore, we tested the effect of blockade of RANK-L with OPG on the development of ovalbumin (OVA)-induced airway allergic inflammation (AAI) and accompanying immune response. The absolute counts of CD11chighCD11b+CD103− (CD11b+) dendritic cells (DC), ST2+Foxp3−CD4+ (Th2) cells and BrdU+(i.e., proliferating)CD4+ T cells were determined in the mediastinal lymph nodes (MLNs) and lungs of untreated non-immunized mice, untreated OVA-immunized mice and OPG-treated OVA-immunized mice. Immunization with OVA induced a significant increase in the mean scores of lung histologic lesions and administration of OPG completely prevented this effect. The absolute counts of CD11b+ DC, Th2 cells and BrdU+CD4+ T cells were increased in the MLNs and lungs of untreated OVA-immunized mice. Treatment with OPG attenuated, but did not abolish, the OVA-induced increase in the count of CD11b+ DC in the MLNs. In turn, administration of this agent prevented the OVA-induced increase in the count of Th2 cells and BrdU+CD4+ T cells in the MLNs and lungs. In conclusion, blockade of RANK/RANKL interaction prevents OVA-induced AAI and this effect is mediated through inhibition the allergen-induced clonal expansion of CD4+ T cells in the MLNs. Clinical implication: the local inhibition of RANK/RANK-L interaction within the respiratory system can be considered as a novel therapeutic strategy in treatment of allergic asthma.