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Dr Hicham Bouabe

Research Interests

Phosphoinositide 3-kinases (PI3Ks) are involved in multiple signaling pathways that regulate different stages and aspects of the life of immune cells: their development, differentiation, effector function, survival, metabolism and motility. One purpose of our work is to understand the role of p110δ, a member of the PI3K family, in the regulation of immune cells, especially CD8 T cells, using transgenic mice, and animal models of infectious, autoimmune and malignant diseases.

We also investigate IL-10-dependent immune regulation. Because of its immunosuppressive function, IL-10 has become widely implicated as a functional marker for immune regulatory cells. Subsequently, the list of ‘regulatory’ cell types has become longer, including regulatory T cells, regulatory B cells, regulatory NK and NKT cells, regulatory DCs, regulatory macrophages, regulatory neutrophils, regulatory myeloid cells and regulatory mast cells.

To enable easy tracking of all IL-10-producing cell subsets, I developed a highly sensitive IL-10-β-lactamase reporter (ITIB) mouse model which easily and dynamically reports IL-10 producing cells, and subsequently enables their functional characterization.

We are using ITIB mice to investigate the molecular mechanisms underlying IL-10 expression regulation by different cells types, and the role of IL-10-producing cells during immune responses using murine models of infectious, malignant and autoimmune diseases.

Keywords

p110δ ; PI3K ; cytotoxic T cells (CTL) ; infection ; IL-10 ; reporter mice ; CD8 T cells ; immune regulatory cells

Key Publications

Ali K, Soond DR, Piñeiro R, Hagemann T, Pearce W, Lim EL, Bouabe H, Scudamore CL, Hancox T, Maecker H, Friedman L, Turner M, Okkenhaug K, Vanhaesebroeck B. Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.
Nature. 2014 Jun 11. doi: 10.1038/nature13444.

Bouabe H, Okkenhaug K. A protocol for construction of gene targeting vectors and generation of homologous recombinant embryonic stem cells. Methods in molecular biology (Clifton, N.J.) 2013; 1064 : 337-54

Bouabe H, Okkenhaug K. Gene targeting in mice: a review. Methods in molecular biology (Clifton, N.J.) 2013; 1064 : 315-36

Kawakami T, Lichtnekert J, Thompson LJ, Karna P, Bouabe H, Hohl TM, Heinecke JW, Ziegler SF, Nelson PJ, Duffield JS. Resident renal mononuclear phagocytes comprise five discrete populations with distinct phenotypes and functions. J Immunol. 2013;191(6):3358-72.

Bouabe H. Cytokine reporter mice: the special case of IL-10. Scand J Immunol. 2012 ;75(6):553-67.

Bouabe H, Liu Y, Moser M, Bösl MR, Heesemann J. Novel highly sensitive IL-10-beta-lactamase reporter mouse reveals cells of the innate immune system as a substantial source of IL-10 in vivo. J Immunol. 2011; 187(6):3165-76.

Bouabe H. Polypeptide Rearrangement Hypothesis and Its Implication in Genetic Diversity. J Proteomics Bioinform (2008). DOI:10.4172/jpb.1000042