Maintenance of tolerance and restoration of host homeostasis following insults relies on a complex and coordinated set of innate and adaptive responses. These tissue tailored responses are controlled by specialized populations of cells that integrate local cues such as defined metabolites or cytokines in order to induce responses in a way that preserve the functional requirements of each tissue. Our work helped to identify some of these tissue specific immunological networks and their role in the development of appropriate and controlled immune responses. More particularly we identified novel mechanisms of regulation in the gastrointestinal tract involving a dialogue between ILC and antigen presenting cells. Our findings also reveal that, following GI infection, control of commensal outgrowth is a highly coordinated process involving both the host response and microbial signals. Notably, emigration of neutrophils to the lumen results in the generation of organized intra-luminal structures that encapsulate commensals and limit their contact with the epithelium. Our data propose that the formation of luminal casts depends upon the high-affinity N-formyl peptide receptor, Fpr1. We are exploring the mechanism by which outgrowth of pathobionts is controlled during infection and the potential involvement of neutrophil extracellular trap and biofilm formation in cast formation.

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4
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2014
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Xu, Mo; Pokrovskii, Maria; Ding, Yi et al. (2018) c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554:373-377
Han, Seong-Ji; Glatman Zaretsky, Arielle; Andrade-Oliveira, Vinicius et al. (2017) White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection. Immunity 47:1154-1168.e6
Buxbaum, Nataliya P; Farthing, Donald E; Maglakelidze, Natella et al. (2017) In vivo kinetics and nonradioactive imaging of rapidly proliferating cells in graft-versus-host disease. JCI Insight 2:
Bouladoux, Nicolas; Hennequin, Clotilde; Malosse, Camille et al. (2017) Hapten-Specific T Cell-Mediated Skin Inflammation: Flow Cytometry Analysis of Mouse Skin Inflammatory Infiltrate. Methods Mol Biol 1559:21-36
Lee, Ha-Na; Tian, Linjie; Bouladoux, Nicolas et al. (2017) Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation. J Clin Invest 127:1905-1917
Carpenter, Andrea C; Wohlfert, Elizabeth; Chopp, Laura B et al. (2017) Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok and LRF. J Immunol 199:1716-1728
Lu, Ying; Zhang, Xianyu; Bouladoux, Nicolas et al. (2017) Zbtb1 controls NKp46+ ROR-gamma-T+ innate lymphoid cell (ILC3) development. Oncotarget 8:55877-55888
Bouladoux, Nicolas; Harrison, Oliver J; Belkaid, Yasmine (2017) The Mouse Model of Infection with Citrobacter rodentium. Curr Protoc Immunol 119:19.15.1-19.15.25
Hand, Timothy W; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K et al. (2016) Linking the Microbiota, Chronic Disease, and the Immune System. Trends Endocrinol Metab 27:831-843
Zhong, Chao; Cui, Kairong; Wilhelm, Christoph et al. (2016) Erratum: Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment. Nat Immunol 17:469

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