Immunity to infection is mediated by T lymphocytes,
specialized cells that use highly evolved recognition elements to
maintain protection against foreign microbes. T lymphocytes differentiate
from a naive state to an effector state. The latter is characterized
by the ability to secrete large amounts of potent molecules, termed
cytokines, that collectively orchestrate and focus the attack against
pathogens. Different types of pathogenic organisms require different
types of immune responses, that are defined by the spectrum of cytokines
produced by the effector T lymphocytes. The most characterized effector
subsets, termed type 1 and type 2 immunity, are associated with host
defense against intracellular and intestinal pathogens, such as viruses
and worms, respectively. In some cases, dysregulation of these type
1 and type 2 responses has been associated with tissue-destructive
inflammatory disease, including autoimmune diseases, and allergy,
respectively. My laboratory uses characterized challenges in inbred
strains of mice to define genetic determinants that underlie the proclivity
to form type 1 or type 2 responses. Understanding the underlying molecular
mechanisms for the generation of these effector T lymphocytes may
provide insights into the genetic susceptibility to infectious and
autoimmune diseases. |
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::205-215.
Mohrs M, K Shinkai, K Mohrs, RM Locksley. 2001. Analysis of type 2 immunity in vivo with a biscistronic IL-4 reporter. Immunity 15:303-311.
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 . 2:842-847.
Shinkai K, M Mohrs, RM Locksley. 2002. Helper T
cells regulate type 2 innate immunity in vivo. Nature 420:825-829.
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.
Veldhoen M, RJ Hocking, CJ Atkins, RM Locksley, B Stockinger. 2006. TGF- B in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179-89.
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.
information last updated July 2006 |
Biomedical Sciences (BMS) Graduate Program
