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 factors and immunological networks and their role in the development of appropriate and controlled immune responses. Notably our work identified mechanisms by which the host acquires tolerance to food antigen and how inflammation disrupt these regulatory pathways. Our current work uncover novel mechanisms of tissue regulation by monocytes and the factors responsible for the induction of these responses. Ly6Chi monocytes in particular can perform multiple roles upon tissue recruitment and the differentiation and effector function of these cells can be shaped by the local tissue environment, both at steady-state and during inflammation. For instances, local acquisition of regulatory mediators, such as IL-10, by recruited monocytes has been described in the healthy gut and inflamed skin, as well as during muscle repair, and Ly6Chi monocytes can give rise to immunosuppressive tumor-associated macrophages during cancer. From these studies, a paradigm has emerged proposing that local tissue signals are largely responsible for the acquisition of appropriate function and fate of Ly6Chi monocytes following tissue entry During this fiscal year we explored if in defined inflammatory settings, discrete signals could differentially alter monocyte function during development prior to the onset of systemic inflammation. We postulated that early education of monocytes may be of particular importance for the tailored control of immune responses at highly reactive sites such as the gut. In this context, we previously identified a dual role for Ly6Chi monocytes during acute intestinal infection with Toxoplasma gondii in limiting responses to commensal microbes and preventing lethal immunopathology. We used this model to examine how and where monocytes become primed for regulatory functions. We found that, contrary to the prevailing paradigm, the capacity of Ly6Chi monocytes to respond to microbial stimuli can be altered during their development and prior to BM egress. These results reveal that functional diversity of monocytes may be imprinted early in development and uncover a role for BM innate lymphoid cells in altering haematopoiesis in order to generate effector cells optimally programmed to control tissue specific immunity.
| 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 |
| 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 |
| 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 |
| 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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