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Although a link between inflammation and haemostasis has been reported in asthma, the interaction mechanism has not been completely elucidated. Here, we investigated the direct link between the mammalian immune and coagulation systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were administered protease or antigens intranasally to induce airway inflammation with or without thrombin inhibitors treatment. The effects of thrombin and its inhibitors on interleukin (IL)\u201033 were investigated both in vivo and in vitro. Peripheral blood mononuclear cells (PBMCs) and plasma from asthma patients are collected to verify the correlation between thrombin and group 2 innate lymphocytes (ILC2s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Low\u2010molecular\u2010weight heparin (LMWH, an indirect inhibitor of thrombin) restrained both papain\u2010 and fungus\u2010induced type 2 immune responses in mice by inhibiting IL\u201033\u00a0cleavage. Upon examining the potential thrombin protease consensus sites, we found that IL\u201033 was directly cleaved by thrombin at specific amino acids (R48 and R106) to generate a mature form of IL\u201033 with potent biological activity. In addition, we found that bivalirudin TFA (a direct inhibitor of thrombin) inhibited a variety of type 2 inflammatory responses, such as those in house dust mite (HDM)\u2010 and ovalbumin (OVA)\u2010mediated pulmonary inflammation models. We found that plasma thrombin\u2010antithrombin complex (TATc) levels in asthma patients were positively associated with the number and function of IL\u201033\u2010responder group 2 innate lymphocytes (ILC2s) among peripheral blood mononuclear cells (PBMCs) from asthma patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The data suggested that thrombin inhibitors administration could be effective in treating lung inflammation by regulating ILC2s via IL\u201033\u00a0maturation, indicating that targeting thrombin is a potential way to treat allergic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15210","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T20:40:06Z","timestamp":1641588006000},"page":"2104-2120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Thrombin cleaves IL\u201033 and modulates IL\u201033\u2010activated allergic lung 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