Tacrolimus (FK506) treatment protects allergen, IL-5, and IL-13-induced mucosal eosinophilia.
Immunology. 2021 Jan 29;:
Authors: Kandikattu HK, Venkateshaiah SU, Verma AK, Mishra A
Eosinophils are a common clinical feature associated with chronic allergic diseases and elemental diets, systemic steroids, anti-IL-5, and anti-IL-13 treatment have shown some therapeutic promise. Herein, we present evidence that pre-and post- intraperitoneal administration of tacrolimus (FK506) is very effective in reducing CCR3/SigleF+ eosinophils in Aspergillus-challenged asthma and EoE, CD2-IL-5 induced global eosinophilia and DOX regulated IL-13 induced asthma. We used flow cytometry, anti-major basic protein (MBP) immunostaining to examine eosinophils in the spleen, bone marrow, BALF, lung, esophagus and intestine. Additionally, we also performed ELISA and Western blot analyses to show that tacrolimus treatment also reduces the levels of eosinophil-specific cytokines IL-4, IL-5, IL-13, TGF-β, eosinophil-specific chemokines Eotaxin-1, Eotaxin-2, and progenitors target RCAN1 mRNA levels. Additionally, the current investigations also show that the TGF-β mediated esophageal and lung fibrosis is also reduced in Aspergillus-challenged, CD2-IL-5 transgenic, and DOX-responsive IL-13 mice. Mechanistically, we show that tacrolimus in vitro treatment inhibited bone marrow derived eosinophil proliferation and viability by promoting eosinophils apoptosis that may be associated with down regulation of RCAN1. Taken together, we provide in vivo and in vitro evidence that tacrolimus ameliorates eosinophil levels and associated pathogenesis in allergen-, IL-5- and IL-13-induced EoE, EG, and asthma pathogenesis. Considering tacrolimus side effects and reactivity to several other drugs, we propose the topical use of tacrolimus for pediatric and low dose oral for adult patients as a novel therapeutic strategy for the clinical trial to reduce mucosal eosinophilia first in steroid-refractory or elemental diet non-responsive adult EoE, EG, and asthma patients.
PMID: 33512727 [PubMed – as supplied by publisher]