Immunobiology
Chougnet Lab

Chougnet Research Lab

The Chougnet Lab is interested in pursuing a research program that is both basic (devoted to unraveling the molecular mechanisms underlying immune dysfunction) as well as translational (aiming towards application of the mechanistic information thereby obtained).

Our major scientific interests are HIV infection and the ontogeny of the human immune system. In addition, due to the many similarities between the immune dysfunction characteristic of chronic progressive HIV infection and that developing during aging, we are developing several research projects on the mechanisms underlying immunosenescence.

A major focus of the laboratory has been to study the homeostasis and function of a critical subset of CD4+ T cells, the regulatory T cells (Treg). Treg are critical to establish and sustain immunological self-tolerance, as well as control aggressive responses to foreign antigens. Importantly, Treg develop very early during the ontogeny of the human infant immune system, and their disappearance and/or dysfunction likely plays a role in several debilitating inflammatory diseases that develop in neonates, particularly in premature babies. Conversely, Treg accumulation during chronic HIV infection or aging plays a role in the immune suppression associated with both processes.

Publications

Jackson, CM; Demmert, M; Mukherjee, S; Isaacs, T; Thompson, R; Chastain, C; Gray, J; Senthamaraikannan, P; Presicce, P; Chetal, K; et al. A potent myeloid response is rapidly activated in the lungs of premature Rhesus macaques exposed to intra-uterine inflammation. Mucosal Immunology. 2022; 15:730-744.

Toth, A; Steinmeyer, S; Kannan, P; Gray, J; Jackson, CM; Mukherjee, S; Demmert, M; Sheak, JR; Benson, D; Kitzmiller, J; et al. Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates. Science Translational Medicine. 2022; 14:eabl8574.

Almanan, M; Raynor, J; Ogunsulire, I; Malyshkina, A; Mukherjee, S; Hummel, SA; Ingram, JT; Saini, A; Xie, MM; Alenghat, T; et al. IL-10-producing Tfh cells accumulate with age and link inflammation with age-related immune suppression. Science Advances. 2020; 6:eabb0806.

Jackson, CM; Mukherjee, S; Wilburn, AN; Cates, C; Lewkowich, IP; Deshmukh, H; Zacharias, WJ; Chougnet, CA. Pulmonary Consequences of Prenatal Inflammatory Exposures: Clinical Perspective and Review of Basic Immunological Mechanisms. Frontiers in Immunology. 2020; 11:1285.

Roland, C; Senthamaraikannan, P; Chougnet, CA; Jobe, AH; Kallapur, SG. 111: IL-1 signaling mediates IL-6 expression at the maternal-fetal interface during intrauterine inflammation (IUI). American Journal of Obstetrics and Gynecology. 2018; 218:s80.

Rueda, CM; Lucia Rodriguez-Perea, A; Moreno-Fernandez, M; Jackson, CM; Melchior, JT; Davidson, WS; Chougnet, CA. High density lipoproteins selectively promote the survival of human regulatory T cells. Journal of Lipid Research. 2017; 58:1514-1523.

Jackson, CM; Wells, CB; Tabangin, ME; Meinzen-Derr, J; Jobe, AH; Chougnet, CA. Pro-inflammatory immune responses in leukocytes of premature infants exposed to maternal chorioamnionitis or funisitis. Pediatric Research. 2017; 81:384-390.

Rueda, CM; Jackson, CM; Chougnet, CA. Regulatory T-Cell-Mediated Suppression of Conventional T-Cells and Dendritic Cells by Different cAMP Intracellular Pathways. Frontiers in Immunology. 2016; 7:216.

Rueda, CM; Presicce, P; Jackson, CM; Miller, LA; Kallapur, SG; Jobe, AH; Chougnet, CA. Lipopolysaccharide-Induced Chorioamnionitis Promotes IL-1-Dependent Inflammatory FOXP3+ CD4+ T Cells in the Fetal Rhesus Macaque. Journal of immunology (Baltimore, Md. : 1950). 2016; 196:3706-3715.

Chougnet, CA; Thacker, RI; Shehata, HM; Hennies, CM; Lehn, MA; Lages, CS; Janssen, EM. Loss of Phagocytic and Antigen Cross-Presenting Capacity in Aging Dendritic Cells Is Associated with Mitochondrial Dysfunction. Journal of immunology (Baltimore, Md. : 1950). 2015; 195:2624-2632.

Raynor, J; Karns, R; Almanan, M; Li, K; Divanovic, S; Chougnet, CA; Hildeman, DA. IL-6 and ICOS Antagonize Bim and Promote Regulatory T Cell Accrual with Age. Journal of immunology (Baltimore, Md. : 1950). 2015; 195:944-952.

Lo, B; Zhang, K; Lu, W; Zheng, L; Zhang, Q; Kanellopoulou, C; Zhang, Y; Liu, Z; Fritz, JM; Marsh, R; et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015; 349:436-440.

Moreno-Fernandez, ME; Joedicke, JJ; Chougnet, CA. Regulatory T Cells Diminish HIV Infection in Dendritic Cells - Conventional CD4(+) T Cell Clusters. Frontiers in Immunology. 2014; 5:199.

Raynor, J; Sholl, A; Plas, DR; Bouillet, P; Chougnet, CA; Hildeman, DA. IL-15 Fosters Age-Driven Regulatory T Cell Accrual in the Face of Declining IL-2 Levels. Frontiers in Immunology. 2013; 4:161.

Moreno-Fernandez, ME; Mauricio Rueda, C; Rusie, LK; Chougnet, CA. Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism. Blood. 2011; 117:5372-5380.

Moreno-Fernandez, ME; Zapata, W; Blackard, JT; Franchini, G; Chougnet, CA. Human regulatory T cells are targets for human immunodeficiency Virus (HIV) infection, and their susceptibility differs depending on the HIV type 1 strain. Journal of Virology. 2009; 83:12925-12933.

Lages, CS; Suffia, I; Velilla, PA; Huang, B; Warshaw, G; Hildeman, DA; Belkaid, Y; Chougnet, C. Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. Journal of immunology (Baltimore, Md. : 1950). 2008; 181:1835-1848.

Nilsson, J; Boasso, A; Velilla, PA; Zhang, R; Vaccari, M; Franchini, G; Shearer, GM; Andersson, J; Chougnet, C. HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood. 2006; 108:3808-3817.

Zhang, R; Lifson, JD; Chougnet, C. Failure of HIV-exposed CD4+ T cells to activate dendritic cells is reversed by restoration of CD40/CD154 interactions. Blood. 2006; 107:1989-1995.

Andersson, J; Boasso, A; Nilsson, J; Zhang, R; Shire, NJ; Lindback, S; Shearer, GM; Chougnet, CA. The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients. Journal of immunology (Baltimore, Md. : 1950). 2005; 174:3143-3147.

Presicce, P; Cappelletti, M; Morselli, M; Ma, F; Senthamaraikannan, P; Protti, G; Nadel, BB; Aryan, L; Eghbali, M; Salwinski, L; et al. Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque. iScience. 2023; 26:108118.

Thomas, AL; Godarova, A; Wayman, JA; Miraldi, ER; Hildeman, DA; Chougnet, CA. Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity. Seminars in Immunology. 2023; 70:101836.

Mahajan, S; Alexander, A; Koenig, Z; Saba, N; Prasanphanich, N; Hildeman, DA; Chougnet, CA; DeFranco, E; Andorf, S; Tilburgs, T. Antigen-specific decidual CD8+ T cells include distinct effector memory and tissue-resident memory cells. JCI insight. 2023; 8:e171806.

Atehortua, L; Morris, J; Street, SE; Bedel, N; Davidson, WS; Chougnet, CA. Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes. Journal of Lipid Research. 2023; 64:100425.

Wilburn, AN; McAlees, JW; Haslam, DB; Graspeuntner, S; Schmudde, I; Laumonnier, Y; Rupp, J; Chougnet, CA; Deshmukh, H; Zacharias, WJ; et al. Delayed Microbial Maturation Durably Exacerbates Th17-driven Asthma in Mice. American Journal of Respiratory Cell and Molecular Biology. 2023; 68:498-510.

Doll, JR; Moreno-Fernandez, ME; Stankiewicz, TE; Wayland, JL; Wilburn, A; Weinhaus, B; Chougnet, CA; Giordano, D; Cappelletti, M; Presicce, P; et al. BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth. Cell Reports. 2023; 42:112352.

Thomas, AL; Wayman, JA; Almanan, M; Bejjani, AT; Miraldi, ER; Chougnet, CA; Hildeman, DA. Elevated CD153 Expression on Aged T Follicular Helper Cells is Vital for B cell Responses. 2023; 4:2023.03.17.533214.

Wayman, JA; Thomas, A; Bejjani, A; Katko, A; Almanan, M; Godarova, A; Korinfskaya, S; Cazares, TA; Yukawa, M; Kottyan, LC; et al. An atlas of gene regulatory networks for memory CD4 + T cells in youth and old age. 2023; 4:2023.03.07.531590.

Atehortua, L; Baig, M; Morris, J; Trentman, S; Davidson, WS; Fichtenbaum, CJ; Chougnet, CA. Impaired response of memory Treg to high density lipoproteins is associated with intermediate/high cardiovascular disease risk in persons with HIV. Frontiers in Immunology. 2023; 14:1146624.

Feria, MG; Chang, C; Ticona, E; Moussa, A; Zhang, B; Ballena, I; Azañero, R; Ticona, C; De Cecco, CN; Fichtenbaum, CJ; et al. Pro-Inflammatory Alterations of Circulating Monocytes in Latent Tuberculosis Infection. Open Forum Infectious Diseases. 2022; 9:ofac629.

Thomas, AL; Lehn, MA; Janssen, EM; Hildeman, DA; Chougnet, CA. Naturally-aged microglia exhibit phagocytic dysfunction accompanied by gene expression changes reflective of underlying neurologic disease. Scientific Reports. 2022; 12:19471.

Schmidt, AF; Schnell, DJ; Eaton, KP; Chetal, K; Kannan, PS; Miller, LA; Chougnet, CA; Swarr, DT; Jobe, AH; Salomonis, N; et al. Fetal maturation revealed by amniotic fluid cell-free transcriptome in rhesus macaques. JCI insight. 2022; 7:e162101.

Lingel, I; Wilburn, AN; Hargis, J; McAlees, JW; Laumonnier, Y; Chougnet, CA; Deshmukh, H; König, P; Lewkowich, IP; Schmudde, I. Prenatal antibiotics exposure does not influence experimental allergic asthma in mice. Frontiers in Immunology. 2022; 13:937577.

Stevens, J; Steinmeyer, S; Bonfield, M; Peterson, L; Wang, T; Gray, J; Lewkowich, I; Xu, Y; Du, Y; Guo, M; et al. The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota. Science Translational Medicine. 2022; 14:eabl3981.

Atehortua, LM; Street, S; Davidson, WS; D'Alessandro, A; Chougnet, C. Apolipoprotein E enhance survival of effector memory regulatory T lymphocytes by regulating caspase-dependent apoptosis and lipid metabolism. Journal of immunology (Baltimore, Md. : 1950). 2022; 208:56.01.

Jackson, CM; Demmert, M; Mukherjee, S; Isaacs, T; Thompson, R; Chastain, C; Gray, J; Senthamaraikannan, P; Presicce, P; Chetal, K; et al. A potent myeloid response is rapidly activated in the lungs of premature Rhesus macaques exposed to intra-uterine inflammation. Mucosal Immunology. 2022; 15:730-744.

Toth, A; Steinmeyer, S; Kannan, P; Gray, J; Jackson, CM; Mukherjee, S; Demmert, M; Sheak, JR; Benson, D; Kitzmiller, J; et al. Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates. Science Translational Medicine. 2022; 14:eabl8574.

van der Heijden, YF; Zhang, B; Chougnet, CA; Huaman, MA. Cytomegalovirus Infection Is Associated With Increased Prevalence of Latent Tuberculosis Infection. Open Forum Infectious Diseases. 2021; 8:ofab539.

Thomas, AL; Alarcon, PC; Divanovic, S; Chougnet, CA; Hildeman, DA; Moreno-Fernandez, ME. Implications of Inflammatory States on Dysfunctional Immune Responses in Aging and Obesity. Frontiers in Aging. 2021; 2:732414.

Cappelletti, M; Presicce, P; Feiyang, M; Senthamaraikannan, P; Miller, LA; Pellegrini, M; Sim, MS; Jobe, AH; Divanovic, S; Way, SS; et al. The induction of preterm labor in rhesus macaques is determined by the  strength of immune response to intrauterine infection. Editor, Smith GC. PLoS biology. 2021; 19:e3001385.

Moreno-Fernandez, ME; Sharma, V; Stankiewicz, TE; Oates, JR; Doll, JR; Damen, MS M A; Almanan, MA T A; Chougnet, CA; Hildeman, DA; Divanovic, S. Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner. Nutrition and Diabetes. 2021; 11:15.

Schmidt, AF; Kannan, PS; Bridges, J; Presicce, P; Jackson, CM; Miller, LA; Kallapur, SG; Chougnet, CA; Jobe, AH. Prenatal inflammation enhances antenatal corticosteroid-induced fetal lung maturation. JCI insight. 2020; 5:e139452.

Almanan, M; Raynor, J; Ogunsulire, I; Malyshkina, A; Mukherjee, S; Hummel, SA; Ingram, JT; Saini, A; Xie, MM; Alenghat, T; et al. IL-10-producing Tfh cells accumulate with age and link inflammation with age-related immune suppression. Science Advances. 2020; 6:eabb0806.

Jackson, CM; Mukherjee, S; Wilburn, AN; Cates, C; Lewkowich, IP; Deshmukh, H; Zacharias, WJ; Chougnet, CA. Pulmonary Consequences of Prenatal Inflammatory Exposures: Clinical Perspective and Review of Basic Immunological Mechanisms. Frontiers in Immunology. 2020; 11:1285.

Toothaker, JM; Presicce, P; Cappelletti, M; Stras, SF; McCourt, CC; Chougnet, CA; Kallapur, SG; Konnikova, L. Immune Cells in the Placental Villi Contribute to Intra-amniotic Inflammation. Frontiers in Immunology. 2020; 11:866.

Jain, VG; Kong, F; Kallapur, SG; Presicce, P; Senthamaraikannnan, P; Cappelletti, M; Chougnet, CA; Bhattacharyya, S; Pasare, C; Muglia, LJ. IRAK1 Is a Critical Mediator of Inflammation-Induced Preterm Birth. Journal of immunology (Baltimore, Md. : 1950). 2020; 204:2651-2660.

Presicce, P; Cappelletti, M; Senthamaraikannan, P; Ma, F; Morselli, M; Jackson, CM; Mukherjee, S; Miller, LA; Pellegrini, M; Jobe, AH; et al. TNF-Signaling Modulates Neutrophil-Mediated Immunity at the Feto-Maternal Interface During LPS-Induced Intrauterine Inflammation. Frontiers in Immunology. 2020; 11:558.

Fisher, AL; Sangkhae, V; Presicce, P; Chougnet, CA; Jobe, AH; Kallapur, SG; Tabbah, S; Buhimschi, CS; Buhimschi, IA; Ganz, T; et al. Fetal and amniotic fluid iron homeostasis in healthy and complicated murine, macaque, and human pregnancy. JCI insight. 2020; 5:135321.

Itoh, A; Ortiz, L; Kachapati, K; Wu, Y; Adams, D; Bednar, K; Mukherjee, S; Chougnet, C; Mittler, RS; Chen, Y; et al. Soluble CD137 Ameliorates Acute Type 1 Diabetes by Inducing T Cell Anergy. Frontiers in Immunology. 2019; 10:2566.

Ryan, RM; Keller, RL; Poindexter, BB; D'Angio, CT; Shaw, PA; Bellamy, SL; Moore, PE; McPherson, C; Greenberg, JM; Chougnet, C; et al. Respiratory Medications in Infants <29 Weeks during the First Year Postdischarge: The Prematurity and Respiratory Outcomes Program (PROP) Consortium. The Journal of Pediatrics. 2019; 208:148-155.e3.

Ryan, RM; Feng, R; Bazacliu, C; Ferkol, TW; Ren, CL; Mariani, TJ; Poindexter, BB; Wang, F; Moore, PE; Chougnet, C; et al. Black Race Is Associated with a Lower Risk of Bronchopulmonary Dysplasia. The Journal of Pediatrics. 2019; 207:130-135.e2.

Science Blog

Claire Chougnet Named as Inaugural Margaret K. Hostetter Endowed Chair
Autoimmune Disorders

Claire Chougnet Named as Inaugural Margaret K. Hostetter Endowed Chair

Claire A. Chougnet, PhD8/3/2021

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Claire A. Chougnet, PhD  
Phone: 513-636-8847
Email: claire.chougnet@cchmc.org
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