Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance

• DOI: 10.1084/jem.20121849
• Publication Date: 2013-04-02T01:10:07Z
• Authors: Pejman Soroosh; Taylor A. Doherty; Wei Duan; Amit Kumar Mehta; Heonsik Choi; Yan Fei Adams; Zbigniew Mikulski; Naseem Khorram; Peter Rosenthal; David H. Broide; Michael Croft
• Keywords: Adoptive Cell Transfer

Airway tolerance is the usual outcome of inhalation harmless antigens. Although T cell deletion and anergy are likely components tolerogenic mechanisms in lung, increasing evidence indicates that antigen-specific regulatory cells (inducible Treg [iTreg cells]) express Foxp3 also critical. Several lung antigen-presenting have been suggested to contribute tolerance, including alveolar macrophages (MØs), classical dendritic (DCs), plasmacytoid DCs, but whether these possess attributes required directly promote development Foxp3+ iTreg unclear. Here, we show lung-resident tissue MØs coexpress TGF-β retinal dehydrogenases (RALDH1 RALDH 2) under steady-state conditions their sampling airborne antigen presentation CD4 resulted generation cells. induction this model depended on both retinoic acid. Transfer antigen-pulsed into airways correspondingly prevented asthmatic inflammation upon subsequent challenge with antigen. Moreover, exposure allergens suppressed ability generate coincident blocking airway tolerance. Suppression proteases TLR-mediated signals. Therefore, functions, strategies target might hold promise for prevention or treatment allergic asthma.