| First Author | Gahring LC | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 3 | Pages | e57481 |
| PubMed ID | 23469197 | Mgi Jnum | J:199854 |
| Mgi Id | MGI:5505382 | Doi | 10.1371/journal.pone.0057481 |
| Citation | Gahring LC, et al. (2013) Nicotinic receptor alpha7 expression identifies a novel hematopoietic progenitor lineage. PLoS One 8(3):e57481 |
| abstractText | How inflammatory responses are mechanistically modulated by nicotinic acetylcholine receptors (nAChR), especially by receptors composed of alpha7 (alpha7) subunits, is poorly defined. This includes a precise definition of cells that express alpha7 and how these impact on innate inflammatory responses. To this aim we used mice generated through homologous recombination that express an Ires-Cre-recombinase bi-cistronic extension of the endogenous alpha7 gene that when crossed with a reporter mouse expressing Rosa26-LoxP (yellow fluorescent protein (YFP)) marks in the offspring those cells of the alpha7 cell lineage (alpha7(lin+)). In the adult, on average 20-25 percent of the total CD45(+) myeloid and lymphoid cells of the bone marrow (BM), blood, spleen, lymph nodes, and Peyers patches are alpha7(lin+), although variability between litter mates in this value is observed. This hematopoietic alpha7(lin+) subpopulation is also found in Sca1(+)cKit(+) BM cells suggesting the alpha7 lineage is established early during hematopoiesis and the ratio remains stable in the individual thereafter as measured for at least 18 months. Both alpha7(lin+) and alpha7(lin-) BM cells can reconstitute the immune system of naive irradiated recipient mice and the alpha7(lin+):alpha7(lin-) beginning ratio is stable in the recipient after reconstitution. Functionally the alpha7(lin+):alpha7(lin-) lineages differ in response to LPS challenge. Most notable is the response to LPS as demonstrated by an enhanced production of IL-12/23(p40) by the alpha7(lin+) cells. These studies demonstrate that alpha7(lin+) identifies a novel subpopulation of bone marrow cells that include hematopoietic progenitor cells that can re-populate an animal's inflammatory/immune system. These findings suggest that alpha7 exhibits a pleiotropic role in the hematopoietic system that includes both the direct modulation of pro-inflammatory cell composition and later in the adult the role of modulating pro-inflammatory responses that would impact upon an individual's lifelong response to inflammation and infection. |
