Each microenvironment is controlled by a specific set of regulatory and effector elements that have to be finely and constantly tuned to maintain local homeostasis. These environments could be site specific, such as the gut environment, or induced by chronic exposure to microbes. Our laboratory aim at understanding the site-specific and cell-specific factors controlling the induction of defined regulatory of effector responses. In particular we are exploring, 1- The factors controlling Treg cell induction, function and stability, 2- the role of mucosa tissue resident cells such as eosinophils in controlling immune responses and 3- the role of the mucosa antigen pressing cell network in controlling regulatory and effector responses. 1- Our work previously showed that regulatory T cells (Treg) can play in important role in the control of effector responses against pathogens and in the control of microbial persistence. Treg cells are also important in the gastrointestinal tract via their control of harmful immune responses. The capacity of Treg cells to properly function relies on their ability to accumulate at inflamed sites and appropriately adapt to their local environment. We identified novel factors controlling the induction, function and stability of Treg cells at mucosal sites in the context of microbial infection. 2- Eosinophils are resident immune cells of the healthy gastrointestinal (GI) tract. Once considered exclusively inflammatory cells that support allergic (Th2) inflammation, recent evidence demonstrates a role for eosinophils in supporting a more broad set of inflammatory responses. Indeed, eosinophils are a component of both active and inactive lesions in inflammatory bowel disease (IBD). Although eosinophils become activated upon entry into tissues, the factors controlling their homeostasis and the consequences of eosinophil activation in the GI tract remain enigmatic. Our studies have begun to elucidate novel pathways of eosinophil activation in the GI tract and the role of eosinophils in contributing to effector immune responses in this environment. 3- Surviving infection by a highly virulent pathogen requires the rapid development of a regulated inflammatory response. Failure to respond swiftly can lead to high parasitemia, while too exuberant an immune response can lead to mortality as a result of severe immunopathology. The balance between inflammation and regulation is particularly important in the gut where we have identified multiple mechanisms involving antigen-presenting cells and regulatory T cells that operate at steady-state to limit aberrant responses to food or commensal antigens. However, relatively little is known about how this mucosal regulatory network is remodeled in the context of pathogen challenge, and whether alternative mechanisms of suppression are ultimately employed to limit immune responses. We have identified novel mechanisms of regulation employed by resident and recruited APC populations in the context of acute infection.
| 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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