Early pubertal maturation and risk of childhood asthma: A mendelian randomization and longitudinal study
Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, we investigated the role of PGRN in allergic airway inflammation.
Production of PGRN and various type 2 cytokines were evaluated in mouse airways exposed to house dust mite allergen and main cellular sources of these molecules were investigated using in macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage derived PGRN-deficient mice and NKT cell knock out mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation.
PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRNdeficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period.
The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.
Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
Jun-Pyo Choi, So Young Park, Keun-Ai Moon, Eun Hee Ha, Yeon Duk Woo, Doo Hyun Chung, Hyouk-Soo Kwon, Tae-Bum Kim, Hae-Sim Park, Hee-Bom Moon, Woo-Jung Song and You Sook Cho