| First Author | Hoeman CM | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 12 | Pages | 6155-63 |
| PubMed ID | 23650613 | Mgi Jnum | J:204760 |
| Mgi Id | MGI:5543326 | Doi | 10.4049/jimmunol.1202207 |
| Citation | Hoeman CM, et al. (2013) Developmental expression of IL-12Rbeta2 on murine naive neonatal T cells counters the upregulation of IL-13Ralpha1 on primary Th1 cells and balances immunity in the newborn. J Immunol 190(12):6155-63 |
| abstractText | Upon exposure to Ag on the day of birth, neonatal mice mount balanced primary Th1 and Th2 responses, with the former displaying upregulated IL-13Ralpha1 expression. This chain associates with IL-4Ralpha to form a heteroreceptor (IL-4Ralpha/IL-13Ralpha1) that marks the Th1 cells for death by IL-4 produced by Th2 cells during rechallenge with Ag, hence the Th2 bias of murine neonatal immunity. The upregulation of IL-13Ralpha1 on neonatal Th1 cells was due to the paucity of IL-12 in the neonatal environment. In this study, we show that by day 8 after birth, naive splenic T cells are no longer susceptible to IL-13Ralpha1 upregulation even when exposed to Ag within the neonatal environment. Furthermore, during the 8-d lapse, the naive splenic T cells spontaneously and progressively upregulate the IL-12Rbeta2 chain, perhaps due to colonization by commensals, which induce production of IL-12 by cells of the innate immune system such as dendritic cells. In fact, mature T cells from the thymus, a sterile environment not accessible to microbes, did not upregulate IL-12Rbeta2 and were unable to counter IL-13Ralpha1 upregulation. Finally, the 8-d naive T cells were able to differentiate into Th1 cells even independently of IL-12 but required the cytokine to counter upregulation of IL-13Ralpha1. Thus, in neonatal mice, IL-12, which accumulates in the environment progressively, uses IL-12Rbeta2 to counter IL-13Ralpha1 expression in addition to promoting Th1 differentiation. |
