Javier Rangel-Moreno, Ph.D. Lab
Javier Rangel-Moreno, Ph.D.
University of Rochester School of Medicine and Dentistry
Division of Allergy/Immunology and Rheumatology
Cooperation between the cellular and humoral arms of the immune system is necessary for efficient control of the influenza infection and resolution of the inflammatory response in the inflamed lungs. It is accepted that CD8 T cells are important cells for the clearance of infected cells, although there is information that supports the relevance of CD4 T cell help in the generation of efficient generation of cytotoxic CD8 T cells. In addition, CD4 T cells are important for the production of isotype-switched antibodies, which neutralize viruses and prevent the infection of epithelial cells. Also, it is known that early imprinting of immune cells during neonatal life changes immunity generated against aerial pathogens in the adult life. Therefore, I will investigate the impact of neonate mice irradiation on the induction of pulmonary immunity against influenza infection. Our hypothesis is that early irradiation can cause defects on local immunity, which will compromise the control of the pulmonary viral infection. In this project, we will evaluate the defects in cellular and humoral immunity of adult mice previously exposed to sublethal irradiation at neonatal age. Understanding the defects on specific cell populations or molecular pathways can help to first design mitigation strategies to restore protective immunity in irradiated mice, which will potentially have a practical application in the human arena.
In the normal prostate, there is formation of tertiary lymphoid organs (TLO) that are collectively known as prostate associated lymphoid tissue (PALT). Interestingly, in prostate intraepithelial neoplasia (PIN), prostate cancer and prostate tissue from patients with spontaneous cancer regression, TLO are still present. Generally, TLO are associated to the generation of local immunity, accelerating clearance of pathogens or exacerbating pathological responses. Although the presence of TLO in the prostate is suggestive of an active immune response, I will characterize the tumor environment to find molecular or cellular evidence of protective immunity, especially in unique samples from patients with spontaneous tumor regression. In this study, I will be focused to analyze the tumor environment in autopsies from patients with prostate cancer. The global idea is to find markers (cytokines, lymphocyte populations, stromal cells) that can explain the spontaneous regression in prostate cancer, which could be used as prognostic markers or potentially as adjuvants for prostate cancer immunotherapy.
Khader SA, Gugliani L, Rangel-Moreno J, Gopal R, Junecko BA, Fountain JJ, Martino C, Pearl JE, Tighe M, Lin YY, Slight S, Kolls JK, Reinhart TA, Randall TD and Cooper AM. IL-23 is required for long-term control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung. J immunol 187(10): 5402-5407: 2011.
Rangel-Moreno Javier, Carragher DM, de la Luz Garcia-Hernandez M, Hwang JY, Kusser K, Hartson L, Kolls JK, Khader SA and Randall TD. The development of inducible bronchus-associated lymphoid tissue depends on IL17. Nat Immunol 12(7): 639-646: 2011.
Kang DD, Lin Y, Moreno JR, Randall TD and Khader SA.Profiling early immune responses in the mouse model of tuberculosis. Plos One 6(1): e16161: 2011.
Zhang S, Rozell M, Verma RK, Albu DI, Califano D, VanValkenburgh J, Merchant A, Rangel-Moreno J, Randall TD, Jenkins NA, Copeland NG, Liu P and Avram D. Antigen specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b.J Exp Med 207(8): 1687-1699: 2010.
Cruz A, Fraga AG, Fountain JJ, Rangel-Moreno J, Torrado E, Saraiva M, Pereira DR, Randall TD, Pedrosa J, Cooper AM and Castro AG. Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis. J Exp Med 207(8): 1609-1612: 2010.
Chiavolini D, Rangel-Moreno J, Berg G, Christian K, Oliveira-Nascimento L, Weir S, Alroy J, Randall TD and Wetzler LM. Bronchus-associated lymphoid tissue (BALT) and survival in a vaccine mouse model of tularemia. Plos One 5(6): e11156: 2010