LPS-induced CD11b+Gr1(int)F4/80+ regulatory myeloid cells suppress allergen-induced airway inflammation.
LPS-induced CD11b+Gr1(int)F4/80+ regulatory myeloid cells suppress allergen-induced airway inflammation.
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DOI：
10.1016/j.intimp.2011.01.034
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发表时间：
2011-07
影响因子：
5.6
通讯作者：
Ray P
中科院分区：
文献类型：
--
作者：
Arora M;Poe SL;Ray A;Ray P
In humans, the bacterial product lipopolysaccharide (LPS) has been associated with protection from allergic diseases such as asthma. However, in mouse models of allergic asthma, differential effects of LPS have been noted based on the dose. A low dose of LPS promotes Th2 responses and allergic disease but a high dose has been associated with suppression of allergic airway inflammation. Our recent work has described the ability of LPS to increase the frequency of CD11b+Gr1intF4/80+ (abbreviated as Gr1int cells) cells in the lung tissue of mice in a dose-dependent fashion that is dependent on TLR4 and the TLR adaptor protein, MyD88. Both phenotypically and morphologically, the cells were found to have similarities with myeloid-derived suppressor cells. Adoptive transfer of LPS-induced Gr1int cells suppressed allergen-induced airway inflammation suggesting that these myeloid cells may have regulatory functions in allergic asthma. Although the Gr1int cells are readily detectable in the lung tissue of LPS-treated mice, they are barely detectable in the lung-draining lymph nodes (LNs) or in the airway lumen. This causes selective enrichment of these cells over dendritic cells (DCs) in the tissue since migratory DCs are induced by LPS to migrate to the draining LNs for presentation of antigen to LN T cells. The Gr1int cells were found to blunt the ability of lung DCs to upregulate GATA-3 or to promote STAT5 activation in primed Th2 cells, both transcription factors having critical roles in Th2 effector function. Thus, a complete understanding of the generation and regulation of the Gr1int cells would provide new avenues to either promote or delete these cells for disease-specific immunoregulation.
