The Immunosuppressive Functions of Two Novel Tick serpins, HlSerpin-a and HlSerpin-b, from Haemaphysalis longicornis.

In this study, we reported the cloning and functional characterizations of two novel serpin genes, HlSerpin-a and HlSerpin-b, from the hard tick Haemaphysalis longicornis of China. Recombinant HlSerpin-a and HlSerpin-b displayed protease inhibitory activities against multiple mammalian proteases. Similar to other tick serpins, HlSerpin-a and HlSerpin-b suppressed the expression of inflammatory cytokines such as TNF-α, IL6 and IL-1β from LPS stimulated mouse bone marrow-derived macrophages (BMDMs) or mouse bone marrow-derived dendritic cells (BMDCs). The minimum active region (Reaction Centre Loop) of HlSerpin-a, named SA-RCL, showed similar biological activities as HlSerpin-a in the protease inhibition and immune suppression assays. The immunosuppressive activities of full length HlSerpin-a and SA-RCL are impaired in Cathepsin G or Cathepsin B knockout mouse macrophages, suggesting that the immunomodulation function of SA and SA-RCL are dependent on their protease inhibitory activity. Finally, we showed that both full length HlSerpins and SA-RCL can relieve the joint swelling and inflammatory response in collagen-induced mouse arthritis models. These results suggested that HlSerpin-a and HlSerpin-b are two functional arthropod serpins, and the minimal reactive peptide SA-RCL is a potential candidate for drug development against inflammatory diseases. PMID: 31606893 [PubMed - as supplied by publisher]
Source: Immunology - Category: Allergy & Immunology Authors: Tags: Immunology Source Type: research