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Interstitial Lung Disease

Granulomatous Lung Disease

HIV disease

Pulmonary Clinic

Clinic Location:

University of Colorado Hospital

12605 E 16th Ave.

Aurora, CO 80045

Clinic Days:

Tuesday Afternoons

Appointment Contact:

720-848-0748

For more information please see Dr. Fontenot's profile at CUDoctors.com.

The interests of the laboratory are diverse, but mainly center on the role of T cells in the development of lung disease. In particular, the laboratory is interested in determining the mechanism by which CD4+ T cells recognize the beryllium antigen in the context of HLA-DP2. We have recently determined the structure of HLA-DP2 and this structure defines a potential beryllium binding site. The immunologic mechanisms involved in the progression from beryllium sensitization and disease as well as the development of biomarkers that could potentially detect this progression in the absence of invasive procedures is also a major interest.

We are also interested in the alterations in the lung microbiome that characterize the lung in different stages of HIV disease and whether a broadened microbiome could contribute to the early onset of lung disease in HIV-infected patients.

Research Team:

Michael Falta, PhD

Doug Mack, PhD

Allison Martin, BS

Natalie Bowerman, PhD

Fontenot AP, Keizer TS, McCleskey M, Mack DG, Meza-Romero R, Chou YK, Vandenbark AA, Scott B, and Burrows GG. Recombinant HLA-DP2 binds beryllium and tolerizes beryllium-specific pathogenic T cells.  J. Immunol. 2006; 177:3874-3883.

Simonian PL, Roark CL, Diaz del Valle F, Palmer BE, Douglas I, Ikuta K, Born WK, O’Brien RL, and Fontenot AP. Role of γδ T cells in the recruitment of CD4⁺ and CD8⁺ T cells to lung and subsequent pulmonary fibrosis. J. Immunol. 2006; 177:4436-4443.

Mack CL, Tucker RM, Lu BR, Sokol RJ, Fontenot AP, Ueno Y, and Gill RG. Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia. Hepatology 2006; 44:1231-1239.

Sawyer RT, Fontenot AP, Barnes TA, Parsons CE, Tooker BC, Maier LA, Gillespie MM, Gottschall EB, Silveira L, Hagman J, and Newman LS. Beryllium-induced TNF-α production is transcriptionally-dependent in chronic beryllium disease. Am. J. Respir. Cell Mol. Biol. 2007; 36:191-200.

Mack CL, Falta MT, Sullivan AK, Karrar F, Freed BM, Sokol RJ, and Fontenot AP. Oligoclonal expansions of CD4⁺ and CD8⁺ T cells in the liver and bile duct of biliary atresia patients. Gastroenterology 2007; 133:278-287.

Palmer BE, Mack DG, Martin AK, Maier LA, and Fontenot AP. CD57 expression correlates with alveolitis severity in subjects with beryllium-induced disease. J. Allergy Clin. Immunol. 2007; 120:184-191.

D’Souza M, Fontenot AP, Mack DG, Lozupone CA, Dillon S, Meditz A, Wilson CC, Connick E, and Palmer BE. Programmed death 1 expression on HIV-specific CD4⁺ T cells is driven by HIV replication and is associated with T cell dysfunction. J. Immunol. 2007; 179:1979-1987.

Palmer BE, Mack DG, Martin AK, Gillespie, M, Mroz MM, Maier LA, and Fontenot AP. Up-regulation of programmed death-1 expression on beryllium-specific CD4⁺ T cells in chronic beryllium disease. J. Immunol. 2008; 180:2704-2712.

Roark CL, Simonian PL, Fontenot AP, Born WK, and O’Brien RL. γδ T cells: an important source of IL-17.  Curr. Opin. Immunol. 2008; 20:353-357.

Mack DG, Martin AK, Palmer BE, Maier LA, Watts TH, and Fontenot AP. 4-1BB enhances proliferation of beryllium-specific T cells in the lung of subjects with chronic beryllium disease. J. Immunol. 2008; 181:4381-4388.

Fontenot AP and Amicosante M. Metal-induced diffuse lung disease. Sem. Respir. Crit. Care. 2008; 29:662-669.

Simonian PL, Roark CL, Lanham AL, Born WK, O’Brien RL, and Fontenot AP. Th17 Polarized Immune Response in a Murine Model of Hypersensitivity Pneumonitis and Lung Fibrosis. J. Immunol. 2009; 182:657-665.

Simonian PL, Roark CL, Lanham AL, Born WK, O’Brien RL, and Fontenot AP. IL-17A expressing γδ T cells promote bacterial clearance in a murine model of hypersensitivity pneumonitis. J. Immunol. 2009; 182:6540-6549.

Kassu A, D’Souza M, O'Connor BP, Kelly E, Akkina R, Fontenot AP, and Palmer BE. Decreased 4-1BB expression on HIV-specific CD4+ T cells is associated with sustained viral replication and reduced IL-2 production. Clin. Immunol. 2009; 132:234-245.

Mack DG, Martin AK, Palmer BE, Maier LA, and Fontenot AP. CD27 expression on CD4⁺ T cells differentiates effector from regulatory T cell subsets in the lung. J. Immunol. 2009; 182:7317-7324.

Simonian PL, Roark CL, Born WK, O’Brien RL, and Fontenot AP. γδ T cells and Th17 cytokines in hypersensitivity pneumonitis and lung fibrosis. Transl. Res. 2009; 154:222-227.

Born WK, Roark CL, Jin N, Wands JM, Aydintung K, Huang Y, Hahn YS, Simonian PL, Fontenot AP, O’Brien RL. Role of γδ T cells in lung inflammation. Open Immunol. J. 2009; 2:143-150.

Dai S, Murphy GA, Crawford F, Mack DG, Marrack P, Kappler JW, and Fontenot AP. Crystal structure of HLA-DP2:implications for chronic beryllium disease. Proc. Natl. Acad. Sci. U S A In press.

Mack DG, Lanham AM, Falta MT, Palmer BE, Maier LA, and Fontenot AP. Deficient and dysfunctional regulatory T cells in the lungs of chronic beryllium disease subjects. Am. J. Respir. Crit. Care Med. In press.

Recent Book Chapters:

Fontenot AP, Schwarz MI.  Immunologic Lung Disease.  In: Clinical Immunology: Practices and Principles. (Rich RR, Shearer WT, Fleisher TA, Schroeder HW, Weyand CM, Frew AJ, eds) 3rd Edition, Elsevier. 2008: 1053-1071.

Fontenot AP, Newman LS, and Maier LA. Beryllium Disease. In: Interstitial Lung Disease. (Schwarz MI, King TE, Jr. eds) 5^th Edition, B.C. Becker. In Press.

Falta MT, Fontenot AP. Antigen Processing and Presentation. In: Comprehensive Toxicology (McQueen CA, ed) 2^nd Edition, Elsevier. In Press.

Fontenot AP, Simonian PL.  Immune Recognition and Responses.  In: Textbook of Respiratory Medicine.(Mason RJ, Broaddus VC, King TE, Schraufnagel D, Martin TR, Murray JF, Nadel JA, eds) 5^th Edition, Elsevier. In Press.