TRIM37 regulates allergic airway inflammation in a murine model of asthma

Abstract

Abstract Patients with asthma, an allergic airway inflammation disease caused by dysregulation of T helper cell type 2 (TH2), have dramatically increased in the past decades and cost of care is more than 11.3 billion per year. Evidence reveal that activation of pattern recognition receptor (PRR) signaling in both hematopoietic and non-hematopoietic compartment are critical for the development of allergic airway inflammation. TRIM37 is the only member of Tripartite motif (TRIM) family protein that contains TRAF domain, studies indicated that TRIM37 might involve in regulating PRR-, TNFR- and cytokine-mediated signaling pathways suggesting its important role in regulating immune responses. However, whether there is functional impact of TRIM37 on the development of asthma remains to be examined. Using immunohistochemistry staining of lung tissues from naïve and allergen-induced inflamed mice, positive staining of TRIM37 was observed in airway epithelial cells. Interestingly, the expression level was further augmented when lung was inflamed. Functional analysis of TRIM37 indicated that TRIM37 was involved in regulating TLR-mediated signaling in airway epithelial cells, as production of pro-inflammatory cytokines was reduced in response to TLR agonists when TRIM37 was knocked-down in the cells. Furthermore, when TRIM37 were knocked-down by intratracheally delivering lentivirus carrying TRIM37shRNA into the sensitized mice before challenge showed that knockdown of TRIM37 expression in the lung during challenge diminished cardinal features of asthma. These findings suggested the involvement of TRIM37 in allergic airway inflammation.