T Cells and Development of the Effector Cytokine Repertoire
T cells are the critical effector cells of the adaptive immune response. To acquire effector functions, however, naive T cells undergo a complex differentiation process to become mature cells capable of effecting host defense against microbial pathogens. Different pathogens require different types of effector cells that can have markedly different capabilities. The most widely disparate mature helper T cell populations, termed Th1 and Th2 cells, secrete distinct patterns of cytokines that orchestrate distinct types of immune responses. The laboratory melds molecular and cellular studies to investigate the signals that direct the differentiation of naive CD4+ T cells to their mature states.
The current laboratory interests focus not only of T cell differentiation, but also on the acquisition of cytokine expression by innate cells of the immune system. Using a variety of genetically modified cells and mice, cytokine expression is studied in vitro and in vivo, using both infectious and allergic models. Major interests include understanding the primary regulation of IL-4 gene transcription in both T cells and non-T cells, and in exogenous signals that drive cytokine expression at inflammatory foci.
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Grogan JL, M Mohrs, B Harmon, DA Lacy, JW Sedat, RM Locksley. 2001. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14:205-15.
Mohrs M, K Shinkai, K Mohrs, RM Locksley. 2001. Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter. Immunity 15:303-11.
Mohrs M, CM Blankespoor, ZE Wang, GG Loots, V Afzal, H Hadeiba, K Shinkai, EM Rubin, RM Locksley. 2001. Deletion of a coordinate regulator of type 2 cytokine expression in mice. Nature Immunol. 2:842-7.
Davies SJ, JL Grogan, RB Blank, KC Lim, RM Locksley, JH McKerrow. 2001. Modulation of blood fluke development in the liver by unconventional hepatic CD4+ lymphocytes. Science 294:1358-61.
Stetson DB, M Mohrs, V Mallet-Designe, L Teyton, RM Locksley. 2002. Rapid expansion and IL-4 expression by Leishmania-specific naive helper T cells in vivo. Immunity 17:191-200.
Shinkai, K., M. Mohrs, RM Locksley. 2002. Helper T cells regulate eosinophil degranulation in vivo. Nature 420:825-9.
Stetson DB, M Mohrs, RL Reinhardt, JL Baron, ZE Wang, J Gapin, M Kronenberg, RM Locksley. 2003. Constitutive cytokine mRNAs mark NK and NK T cells poised for rapid effector function. J Exp Med 198:1069-76.
Xu M, ZE Wang, RM Locksley. 2004. Innate immune responses in peptidoglycan-recognition-protein-L-deficient mice. Mol Cell Biol 24:7949-57.
Voehringer D, K Shinkai, RM Locksley. 2004. Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 20:267-77.
Mohrs K, AE Wakil, N Killeen, RM Locksley, M Mohrs. 2005. A two-step process for cytokine production revealed by IL-4 dual-reporter mice. Immunity 23:419-29.
Scheu S, DB Stetson, RL Reinhardt, JH Leber, M Mohrs, RM Locksley. 2006. Activation of the integrated stress response during T helper cell differentiation. Nature Immunol 7:644-651.
Voehringer D, TA Reese, X Huang, K Shinkai, RM Locksley. 2006. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med 203:1435-1446.
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