| First Author | Banoth B | Year | 2015 |
| Journal | Elife | Volume | 4 |
| PubMed ID | 25905673 | Mgi Jnum | J:274159 |
| Mgi Id | MGI:6205845 | Doi | 10.7554/eLife.05648 |
| Citation | Banoth B, et al. (2015) Stimulus-selective crosstalk via the NF-kappaB signaling system reinforces innate immune response to alleviate gut infection. Elife 4 |
| abstractText | Tissue microenvironment functions as an important determinant of the inflammatory response elicited by the resident cells. Yet, the underlying molecular mechanisms remain obscure. Our systems-level analyses identified a duration code that instructs stimulus specific crosstalk between TLR4-activated canonical NF-kappaB pathway and lymphotoxin-beta receptor (LTbetaR) induced non-canonical NF-kappaB signaling. Indeed, LTbetaR costimulation synergistically enhanced the late RelA/NF-kappaB response to TLR4 prolonging NF-kappaB target gene-expressions. Concomitant LTbetaR signal targeted TLR4-induced newly synthesized p100, encoded by Nfkb2, for processing into p52 that not only neutralized p100 mediated inhibitions, but potently generated RelA:p52/NF-kappaB activity in a positive feedback loop. Finally, Nfkb2 connected lymphotoxin signal within the intestinal niche in reinforcing epithelial innate inflammatory RelA/NF-kappaB response to Citrobacter rodentium infection, while Nfkb2(-/-) mice succumbed to gut infections owing to stromal defects. In sum, our results suggest that signal integration via the pleiotropic NF-kappaB system enables tissue microenvironment derived cues in calibrating physiological responses. |
