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Herein, we present evidence that pre\u2010 and post\u2010intraperitoneal administration of tacrolimus (FK506) is very effective in reducing CCR3\/Siglec\u2010F<jats:sup>+<\/jats:sup> eosinophils in Aspergillus\u2010challenged asthma and EoE, CD2\u2010IL\u20105 induced global eosinophilia, and DOX regulated IL\u201013\u2010induced asthma. We used flow cytometry and anti\u2010major basic protein (MBP) immunostaining to examine eosinophils in the spleen, bone marrow, BALF, lung, oesophagus and intestine. Additionally, we also performed ELISA and Western blot analyses to show that tacrolimus treatment also reduces the levels of eosinophil\u2010specific cytokines IL\u20104, IL\u20105, IL\u201013 and TGF\u2010\u03b2, eosinophil\u2010specific chemokines Eotaxin\u20101 and Eotaxin\u20102, and progenitors of target RCAN1 mRNA and protein levels. Additionally, the current investigations also show that the TGF\u2010\u03b2\u2010mediated oesophageal and lung fibrosis is also reduced in Aspergillus\u2010challenged, CD2\u2010IL\u20105 transgenic and DOX\u2010responsive IL\u201013 mice. Mechanistically, we show that tacrolimus <jats:italic>in vitro<\/jats:italic> treatment inhibited bone marrow\u2010derived eosinophil proliferation and viability by promoting eosinophil apoptosis that may be associated with downregulation of RCAN1. Taken together, we provide <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> evidence that tacrolimus ameliorates eosinophil levels and associated pathogenesis in allergen\u2010, IL\u20105\u2010 and IL\u201013\u2010induced EoE, EG and asthma pathogenesis. Considering tacrolimus side\u2010effects and reactivity to several other drugs, we propose the topical use of tacrolimus for paediatric and low\u2010dose oral for adult patients as a novel therapeutic strategy for the clinical trial to reduce mucosal eosinophilia first in steroid\u2010refractory or elemental diet non\u2010responsive adult EoE, EG and asthma patients.<\/jats:p>","DOI":"10.1111\/imm.13314","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T14:26:53Z","timestamp":1611930413000},"page":"220-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Tacrolimus (FK506) treatment protects allergen\u2010, IL\u20105\u2010 and IL\u201013\u2010induced mucosal eosinophilia"],"prefix":"10.1111","volume":"163","author":[{"given":"Hemanth Kumar","family":"Kandikattu","sequence":"first","affiliation":[{"name":"Department of Medicine Section of Pulmonary Diseases Tulane Eosinophilic 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