Abstract
Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP) that displayed high aldehyde dehydrogenase (ALDH) activity, a rate-limiting step during all-trans retinoic acid (ATRA) synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB) eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.
Highlights
The immune system needs to carefully balance both immune responses and immune tolerance [1]
Previous studies have identified CD11c+ CD11b− dendritic cells (DC) (P1), CD11c+ CD11b+ DC (P2), CD11c− CD11b+ side scatter (SSC)lo Siglec-F− macrophages (P3) and CD11c− CD11b+ SSChi Siglec-F+ eosinophils (P4) in the cells from murine small intestinal lamina propria (LP) (Fig 1A and 1B)[16, 20,21,22]. Of these four subsets from the LP of C57BL/6 mice, an Aldefluor assay confirmed that the CD11cint CD11bhi eosinophils had a significantly higher activity of aldehyde dehydrogenase (ALDH), an indicator for the ability of the cells to produce all-trans retinoic acid (ATRA)[10], than the CD11chi CD11blo DC, CD11chi CD11bhi DC and CD11cint CD11bint macrophages (Fig 1C and 1D)
It has been reported that CD4+CD25+Foxp3+ Treg cells could be induced by the CD103+ DC from mouse mesenteric lymph nodes (MLN) or intestinal LP via a TGF-β1- and ATRA-dependent mechanism[13, 19]
Summary
The immune system needs to carefully balance both immune responses and immune tolerance [1]. Immune responses eliminate harmful antigens such as pathogens and dead or aberrant host cells[1, 2]. Immune tolerance is needed in order to avoid damaging normal host tissues and to allow the presence of harmless antigens such as commensal bacteria and food antigens in the intestinal tract[3]. Regulatory T (Treg) cells play a crucial role in generation and maintenance of immune tolerance[4]. It has been shown that transforming growth factor-beta (TGF-β) stimulates naïve CD4+CD25− T cells to differentiate into either CD4+CD25+Foxp3+ Treg cells or Th17 cells[5, PLOS ONE | DOI:10.1371/journal.pone.0142881. It has been shown that transforming growth factor-beta (TGF-β) stimulates naïve CD4+CD25− T cells to differentiate into either CD4+CD25+Foxp3+ Treg cells or Th17 cells[5, PLOS ONE | DOI:10.1371/journal.pone.0142881 November 20, 2015
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