A Journey to the Intracate Functional Regulation of Eosinophils

The immunological study “NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions” conducted by Assoc. Prof. Dr. Ceren Çıracı Muğan and her lab members from ITU Molecular Biology and Genetics (MBG) Department was published in the journal Immune Network.

Eosinophils which are a variety of white blood cells take place in maintaining the homeostasis in both adaptive and innate immune systems. In addition to their well known functions in parasitic infections and Th2 cell responses, eosinophils carry out many other vital roles for immune system such as protection against bacterial and viral infections as well as anti-inflammation. Nonetheless, how NOD-like receptors (NLRs) and pattern recognition receptors contribute to the eosinophil-mediated immune responses have not been elucidated in detail. According to in vivo experiments performed in this study, after an allergic airway disease model had been induced, it was observed that eosinophil level of NLRC4 deficient mice reduced and Th2 responses mitigated. Results obtained by in vitro experiments using EoL-1 cells indicated that pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3 were promoted evidently upon Toll-like receptor 2 (TLR2) inductions. Besides, secretion of mature IL-1β and cleavage of caspase-1 stemmed from activation by their specific ligands. Intriguingly, afterwards EoL-1 cells had been transfected with small interfering RNAs targeting human NLRC4, Th2 responses like secretions of IL-5 and IL-13 lowered. Expressions of IL-5 receptor and Fc epsilon receptors (FcεR1α, FcεR2) were enhanced by specific induction of NLRC4 with PAM3CSK4 and flagellin. It was striking that NLRC4 inflammasome triggered expression of both costimulatory receptor CD80 and immunoregulatory receptors PD-L1 and Siglec-8, as well. In the study, it was also monitored that NLRC4 upregulation was accompanied by elevated expression and activation of matrix metalloproteinase (MMP)-9, whilst there was no such an increase in MMP-2 expression or activity. All in all, new possible roles of NLRC4  in promoting a myriad of functions fulfilled by eosinophils were proposed in this this scientific work .