The development of LTi cells
ABSTRACT Lymphoid tissue inducer (LTi) cells are programmed by the mammalian fetus to induce the development of lymph nodes and Peyer's patches. LTi cells share a pro-inflammatory profile with Th17 cells, as well as their requirement for the transcription factor RORγt. We discuss here the latest data on the fetal and post-natal development of LTi cells, and their relationship with the larger family of innate lymphoid cells (ILCs). We suggest that the re-programming of RORγt in a subset of common lymphoid progenitors allowed mammals to develop lymphoid organs before birth, whereas other vertebrates only develop such organs in response to infection or injury.
SourceAvailable from: Fabrizio Loiacono[Show abstract] [Hide abstract]
ABSTRACT: Summary Group 3 innate lymphoid cells (ILC3s) are defined by the expression of the transcription factor RORγt, which is selectively required for their development. The lineage-specified progenitors of ILC3s and their site of development after birth remain undefined. Here we identified a population of human CD34+ hematopoietic progenitor cells (HPCs) that express RORγt and share a distinct transcriptional signature with ILC3s. RORγt+CD34+ HPCs were located in tonsils and intestinal lamina propria (LP) and selectively differentiated towards ILC3s. In contrast, RORγt-CD34+ HPCs could differentiate to become either ILC3s or natural killer (NK) cells with differentiation toward ILC3 lineage determined by stem cell factor (SCF) and aryl hydrocarbon receptor (AhR) signaling. Thus, we demonstrate that in humans RORγt+CD34+ cells are lineage-specified progenitors of IL-22+ ILC3s and propose that tonsils and intestinal LP, which are enriched both in committed precursors and mature ILC3s, might represent preferential sites of ILC3 lineage differentiation.Immunity 11/2014; DOI:10.1016/j.immuni.2014.11.010 · 19.75 Impact Factor
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ABSTRACT: The nuclear receptor retinoic acid-related orphan receptor (ROR)γt is required for the generation of Th17 cells, which are involved in various autoimmune diseases, including Sjögren's syndrome (SS). However, the pathological role of RORγt in SS remains to be elucidated. The present study was designed to clarify the role of RORγt in the pathogenesis of sialadenitis-like SS. Histological analysis of RORγt transgenic (Tg) mice was determined, and then Tg mice developed severe spontaneous sialadenitis-like SS. The analysis of infiltrating cells showed that most infiltrating cells were CD4(+) T cells. RORγt-overexpressing CD4(+) T cells induced sialadenitis as a result of transferred CD4(+) T cells from Tg mice into Rag2(-/-) mice. The examination of IL-17-deficient Tg mice indicated that IL-17 was not essential for the development of sialadenitis. The number of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells was significantly decreased in Tg mice, and CD25 expression and IL-2 stimulated STAT5 activation were inhibited in Treg cells. The inhibitory function of Treg cells of Tg mice was equal to that of wild-type mice in vitro. The abundant Treg cells of Tg mice could suppress the development of sialadenitis, but the reduced Treg cells of Tg mice could not inhibit the induction of sialadenitis in Rag2(-/-) mice transferred with effector cells from Tg mice. These results suggest that both RORγt-overexpressed CD4(+) T cells and reduced Treg cells might contribute to the development of SS-like sialadenitis. Copyright © 2014 by The American Association of Immunologists, Inc.
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ABSTRACT: Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. Expected final online publication date for the Annual Review of Immunology Volume 33 is March 21, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.Annual Review of Immunology 01/2015; 33(1). DOI:10.1146/annurev-immunol-032414-112025 · 41.39 Impact Factor