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.
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- "Along this line, extramedullary compartments might represent preferential developmental sites not only for most Group 1 but also for Group 3 ILCs. It has been shown that precursors of murine Group 3 ILCs do not up-regulate RORγt expression in the BM and might migrate very early to the periphery, especially to the intestinal lamina propria (LP), for their development/terminal differentiation (8, 26). However, it still remains an open question at which developmental stage (CLP? "
ABSTRACT: Natural killer (NK) cells are part of the innate lymphoid cell (ILC) family and represent the main cytotoxic population. NK cells develop from bone marrow common lymphoid progenitors and undergo terminal differentiation in the periphery, where they finally gain their cytotoxic competence as well as the ability to produce IFN-γ in response to engagement of activating receptors. This process has been at least partially elucidated and several markers have been identified to discriminate different NK cell stages and other ILC populations. NK cell terminal differentiation is not only associated with progressive phenotypic changes but also with defined effector signatures. In this essay, we will describe the phenotypic and functional characteristics of the main stages of NK cell development and terminal differentiation and discuss them in light of recent discoveries of novel ILC populations.Frontiers in Immunology 12/2013; 4:499. DOI:10.3389/fimmu.2013.00499
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ABSTRACT: As the science of immunology grows increasingly mechanistic, motivation for developing quantitative, design-based engineering approaches has also evolved, both for therapeutic interventions and for elucidating immunological pathways in human disease. This has seeded the nascent field of "immunoengineering," which seeks to apply engineering analyses and design approaches to problems in translational immunology. For example, cell engineers are creating ways to tailor and use immune cells as living therapeutics; protein engineers are devising new methods of rapid antibody discovery; biomaterials scientists are guiding vaccine delivery and immune-cell activation with novel constructs; and systems immunologists are deciphering the evolution and maintenance of T and B cell receptor repertoires, which could help guide vaccine design. The field is multidisciplinary and collaborative, with engineers and immunologists working together to better understand and treat disease. We discuss the scientific progress in this young, yet rapidly evolving research area, which has yielded numerous start-up companies that are betting on impact in clinical and commercial translation in the near future.Science translational medicine 08/2012; 4(148):148rv9. DOI:10.1126/scitranslmed.3003763 · 14.41 Impact Factor
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ABSTRACT: Innate immune and differentiated T cells produce signature cytokines in response to cytokine stimulation. Optimal production requires stimulation by an NF-κB inducer, most commonly an interleukin (IL)-1 family member, and a STAT activator. Usually, there is linkage between the IL-1 family member, the activated STAT and the cytokines produced: IFNγ producers respond to the IL-1 family member, IL-18 and IL-12, a STAT4 activator; IL-13 producers respond to IL-33 (although for ILC2 cells this may be replaced by IL-25) and STAT5 activators; for cells producing IL-17A or IL-22, the combination is IL-1 and a STAT3 inducer. Cytokine-induced cytokine production may have broad significance in orchestrating innate responses to distinct infectious agents and in maintaining inflammatory responses after elimination of the inciting antigen.Trends in Immunology 09/2012; 33(12). DOI:10.1016/j.it.2012.07.006 · 12.03 Impact Factor