| First Author | Kushwah R | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 9 | Pages | 4639-53 |
| PubMed ID | 21948981 | Mgi Jnum | J:179452 |
| Mgi Id | MGI:5302446 | Doi | 10.4049/jimmunol.1101967 |
| Citation | Kushwah R, et al. (2011) Elf3 regulates allergic airway inflammation by controlling dendritic cell-driven T cell differentiation. J Immunol 187(9):4639-53 |
| abstractText | Elf3 belongs to the Ets family of transcription factors and has been implicated in inflammation. Elf3 is highly expressed in the lungs, and Elf3(-/-) mice are impaired in IL-6 production after intranasal LPS exposure. To identify the role of Elf3 in Th17-driven pulmonary inflammation, we have performed epicutaneous sensitization of Elf3(-/-) mice with OVA followed by airway OVA challenge and have identified Elf3(-/-) mice to be impaired in induction of Th17 response, attributable to impairment of IL-6 production by dendritic cells (DCs). However, increased serum levels of OVA-specific IgG1 and IgE were observed, pointing toward an exaggerated Th2 response. To study Th2 response, we performed i.p. sensitization of Elf3(-/-) mice with OVA and confirmed loss of Elf3 to result in an aggravated Th2 response, characterized by increased generation of IL-4-producing T cells, increased levels of OVA-specific IgE and IgG1 Ab titers, and increased serum levels of Th2 cytokines, together with extensive inflammation and mucus production in airways. Elf3(-/-) DCs were impaired in priming Th1 differentiation, which, in turn, promoted Th2 differentiation. This was mediated by the ability of Elf3(-/-) DCs to undergo hypermaturation but secrete significantly lower levels of IL-12 in response to inflammatory stimuli. The impairment of IL-12 production was due to impairment of IL-12p40 gene induction in Elf3(-/-) DCs in response to inflammatory stimuli. Taken together, our study identifies a novel function of Elf3 in regulating allergic airway inflammation by regulating DC-driven Th1, Th2, and Th17 differentiation. |
