| First Author | Heitmann L | Year | 2012 |
| Journal | Am J Pathol | Volume | 181 |
| Issue | 3 | Pages | 897-906 |
| PubMed ID | 22901754 | Mgi Jnum | J:189927 |
| Mgi Id | MGI:5447255 | Doi | 10.1016/j.ajpath.2012.05.032 |
| Citation | Heitmann L, et al. (2012) TGF-beta-responsive myeloid cells suppress type 2 immunity and emphysematous pathology after hookworm infection. Am J Pathol 181(3):897-906 |
| abstractText | Transforming growth factor beta (TGF-beta) regulates inflammation, immunosuppression, and wound-healing cascades, but it remains unclear whether any of these functions involve regulation of myeloid cell function. The present study demonstrates that selective deletion of TGF-betaRII expression in myeloid phagocytes i) impairs macrophage-mediated suppressor activity, ii) increases baseline mRNA expression of proinflammatory chemokines/cytokines in the lung, and iii) enhances type 2 immunity against the hookworm parasite Nippostrongylus brasiliensis. Strikingly, TGF-beta-responsive myeloid cells promote repair of hookworm-damaged lung tissue, because LysM(Cre)TGF-betaRII(flox/flox) mice develop emphysema more rapidly than wild-type littermate controls. Emphysematous pathology in LysM(Cre)TGF-betaRII(flox/flox) mice is characterized by excessive matrix metalloprotease (MMP) activity, reduced lung elasticity, increased total lung capacity, and dysregulated respiration. Thus, TGF-beta effects on myeloid cells suppress helminth immunity as a consequence of restoring lung function after infection. |
