LMP7 Subunit Deficiency of the Immunoproteasome Leads to reduced Th2 Response in OVA/Alum Acute Asthma

LMP7 subunit of the immunoproteasome has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, nothing is known about LMP7 function in Th2 dependent diseases. To study the role of LMP7 in Th2 driven pathology, experimental allergic asthma was selected as a model of the medically relevant disease. We used WT and LMP7-/- knockout (KO) mice of C57BL/6N background for the induction of Alum/OVA, HDM and subcutaneous/OVA acute asthma. We found that LMP7 deficient mice showed reduced OVA/Alum acute asthma characterized by decreased bronchoalveolar lavage (BAL) eosinophilia, OVA specific IgG1 together with low local (BAL) and systemic (OVA reactivated splenocytes) Th2 cytokines. Similarly, lung Th2 cells were also reduced during OVA/Alum asthma while Tregs and Th1/Tc1 cells were not affected. Surprisingly, the proteasome catalytic subunit expression pattern of the lung was not altered during OVA/Alum asthma. Further investigation demonstrated that dendritic cells intrinsic defects were not responsible for the observed phenotype. In contrary to the OVA/Alum model, HDM and subcutaneous OVA induced asthma did not show a significantly reduced Th2 response. Here we show for the first time the role of LPM7 proteasome immunosubunit in the Alum/OVA acute asthma. We demonstrate that LMP7 subunit is necessary for mounting of the strong Th2 response in OVA/Alum model. However, it appears that the observed Th2 defect is not a general trait of LMP7 KO mice as Th2 response was found to be not significantly altered during HDM and adjuvant free subcutaneous/OVA asthma in these mice.