Richard Locksley, MD
The immune system is a complex organization of many cell types whose activities are orchestrated through controlled expression and secretion of cytokines and other mediators. We have produced cytokine reporter mice that allow the visualization of immune system function during a variety of infectious and inflammatory diseases. Our primary interests involve efforts to understand allergic and anti-helminth immunity, which constitute major public health issues in both developed and developing countries. The major goals of the laboratory involve identification of molecular processes that drive eosinophil and basophil responses in tissues; that activate macrophages to the ‘alternatively activated’ state associated with allergic inflammation; that promote the differentiation of Th2 cells in lymph nodes; and that promote T cell help for the induction of the immunoglobulin isotypes IgG1 and IgE associated with allergy.
Selected Publications
*graduate student (present or past)
Mohrs M, *K Shinkai, K Mohrs, RM Locksley. 2001. Analysis of type 2 immunity in vivo with a biscistronic IL-4 reporter. Immunity 15:303-11.
*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 type 2 innate immunity in vivo. Nature 420:825-29.
*Stetson DB, M Mohrs, RL Reinhardt, JL Baron, ZE Wang, L 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.
Voehringer D, *K Shinkai, RM Locksley. 2004. Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 20:267-77.
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.
*Reese TA, H-E Liang, AM Tager, AD Luster, N van Rooijen, D Voehringer, RM Locksley. 2007. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 447:92-96.
Reinhardt RL, H-E Liang, RM Locksley. 2009. Cytokine-secreting follicular T cells shape the antibody repertoire. Nature Immunol 10:385-93.
Sullivan BM, RM Locksley. 2009. Basophils: a nonredundant contributor to host immunity. Immunity 30:12-20.
*Seibold MA, *TA Reese, S Choudhry, MT Salam, K Beckman, C Egn, A Atakilit, K Meade, M Lenoir, HG Watson, S Thyne, R Kumar, KB Weiss, LC Grammar, P Avila, RP Schleimer, JV Fahy, J Rodriguez-Santana, W Rodriguez-Cintron, RG Boot, D Sheppard, FD Gilliland, RM Locksley, EG Burchard. 2009. Differential enzymatic activity of common haplotypic versions of the human acidic mammalian chitinase protein. J Biol Chem 284:19650-58.
Locksley RM. 2010. Asthma and allergic inflammation. Cell 140:777-83.
*Price AE, HE Liang, BM Sullivan, RL Reinhardt, CJ Eisley, DJ Erle, RM Locksley. 2010. Systemically dispersed IL-13-expressing cells in type 2 immunity. 2010. Proc Natl Acad Sci USA 107:11489-94.
Wu D*, AB Molofsky, H-E Liang, RR Ricardo-Gonzalez, HA Jouihan, A Chawla, RM Locksley. 2011. Eosinophils sustain alternatively activated macrophages associated with glucose homeostasis. Science 332:243-247.
Sullivan BM, H-E Liang, JK Bando*, D Wu*, LE Cheng, JK McKerrow, CDC Allen, RM Locksley. 2011. Genetic analysis of basophil function in vivo. Nature Immunol 12:527-535.