Research Projects
PUBLICATIONS
Caillier A, Oleksyn D, Fowell DJ, Miller J, Oakes PW. "T cells use focal adhesions to pull themselves through confined environments." J Cell Biol. 2024 Oct 7; 223(10): e202310067.
Kim D, An L, Moon J, Maymi VI, McGurk AI, Rudd BD, Fowell D, White AC. "Ccr2+ monocyte-derived macrophages influence trajectories of acquired therapy resistance in Braf-mutant melanoma." Cancer research. 2023 May 17; Epub 2023 May 17.
Herman KE, Yoshida T, Hughson A, Grier A, Gill SR, Beck LA, Fowell DJ. "IL-17-Dependent Dysregulated Cutaneous Immune Homeostasis in the Absence of the Wiskott-Aldrich Syndrome Protein." Front Immunol. 2022 Feb 21; 13: 817427.
Bala N, McGurk AI, Zilch T, Rup AN, Carter EM, Leddon SA, Fowell DJ. "T cell activation niches-Optimizing T cell effector function in inflamed and infected tissues." Immunological reviews. 2021 Dec 2; Epub 2021 Dec 02.
Prizant H, Patil N, Negatu S, Bala N, McGurk A, Leddon SA, Hughson A, McRae TD, Gao YR, Livingstone AM, Groom JR, Luster AD, Fowell DJ. "CXCL10 peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter." Cell reports. 2021 Aug 10; 36(6):109523.
Fowell DJ, Kim M. "The spatio-temporal control of effector T cell migration." Nature reviews. Immunology. 2021 Feb 24; Epub 2021 Feb 24.
Bares AJ, Mejooli MA, Pender MA, Leddon SA, Tilley S, Lin K, Dong J, Kim M, Fowell DJ, Nishimura N, Schaffer CB. "Hyperspectral multiphoton microscopy for visualization of multiple, spectrally overlapped fluorescent labels." . 2020 Nov 20; 7(11):1587-1601.
Lim K, Kim TH, Trzeciak A, Amitrano AM, Reilly EC, Prizant H, Fowell DJ, Topham DJ, Kim M. "In situ neutrophil efferocytosis shapes T cell immunity to influenza infection." Nature immunology. 2020 Aug 3; Epub 2020 Aug 03.
Fernandes NRJ, Reilly NS, Schrock DC, Hocking DC, Oakes PW, Fowell DJ. "CD4 T Cell Interstitial Migration Controlled by Fibronectin in the Inflamed Skin." Frontiers in immunology. 2020 11:1501. Epub 2020 Jul 24.
Gaylo-Moynihan A, Prizant H, Popovic M, Fernandes NRJ, Anderson CS, Chiou KK, Bell H, Schrock DC, Schumacher J, Capece T, Walling BL, Topham DJ, Miller J, Smrcka AV, Kim M, Hughson A, Fowell DJ. "Programming of Distinct Chemokine-Dependent and -Independent Search Strategies for Th1 and Th2 Cells Optimizes Function at Inflamed Sites." Immunity. 2019 Aug 20; 51(2):298-309.e6. Epub 2019 Aug 06.
Schrock DC, Leddon SA, Hughson A, Miller J, Lacy-Hulbert A, Fowell DJ. "Pivotal role for ? integrins in sustained Tfh support of the germinal center response for long-lived plasma cell generation." Proceedings of the National Academy of Sciences of the United States of America. 2019 Feb 15; Epub 2019 Feb 15.
Batchu SN, Dugbartey GJ, Wadosky KM, Mickelsen DM, Ko KA, Wood RW, Zhao Y, Yang X, Fowell DJ, Korshunov VA. "Innate Immune Cells Are Regulated by Axl in Hypertensive Kidney." The American journal of pathology. 2018 Aug 0; 188(8):1794-1806.
Oakes PW, Fowell DJ. "CCR7 fuels and LFA-1 grips." Nature immunology. 2018 Jun 0; 19(6):516-518.
Ford J, Hughson A, Lim K, Bardina SV, Lu W, Charo IF, Lim JK, Fowell DJ. "CCL7 Is a Negative Regulator of Cutaneous Inflammation Following Infection." Frontiers in immunology. 2018 9:3063. Epub 2019 Jan 08.
Meli AP, Fontés G, Avery DT, Leddon SA, Tam M, Elliot M, Ballesteros-Tato A, Miller J, Stevenson MM, Fowell DJ, Tangye SG, King IL. "The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance." Immunity. 2016 Oct 18; 45(4):831-846.
Billroth-MacLurg AC, Ford J, Rosenberg A, Miller J, Fowell DJ. "Regulatory T Cell Numbers in Inflamed Skin Are Controlled by Local Inflammatory Cues That Upregulate CD25 and Facilitate Antigen-Driven Local Proliferation." The Journal of immunology: Official journal of the American Association of Immunologists. 2016 Sep 15; 197(6):2208-18. Epub 2016 Aug 10.
Lambert Emo K, Hyun YM, Reilly E, Barilla C, Gerber S, Fowell D, Kim M, Topham DJ. "Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen." PLoS pathogens. 2016 Sep 0; 12(9):e1005881. Epub 2016 Sep 19.
Batchu SN, Hughson A, Wadosky KM, Morrell CN, Fowell DJ, Korshunov VA. "Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension." Arteriosclerosis, thrombosis, and vascular biology. 2016 Aug 0; 36(8):1638-1646. Epub 2016 Jun 30.
Gaylo A, Overstreet MG, Fowell DJ. "Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis." Journal of visualized experiments: JoVE. 2016 Mar 25; (109):e53585. Epub 2016 Mar 25.
Gaylo A, Schrock DC, Fernandes NR, Fowell DJ. "T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning." Frontiers in immunology. 2016 7:428. Epub 2016 Oct 14.
Misra R, Shah S, Fowell D, Wang H, Scheible K, Misra S, Huyck H, Wyman C, Ryan RM, Reynolds AM, Mariani T, Katzman PJ, Pryhuber GS. "Preterm cord blood CD4? T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4? T cells in bronchopulmonary dysplasia." Human immunology. 2015 May 0; 76(5):329-338. Epub 2015 Mar 20.
Shi G, Field DJ, Ko KA, Ture S, Srivastava K, Levy S, Kowalska MA, Poncz M, Fowell DJ, Morrell CN. "Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection." The Journal of clinical investigation. 2014 Feb 0; 124(2):543-52. Epub 2014 Jan 27.
Overstreet MG, Gaylo A, Angermann BR, Hughson A, Hyun YM, Lambert K, Acharya M, Billroth-Maclurg AC, Rosenberg AF, Topham DJ, Yagita H, Kim M, Lacy-Hulbert A, Meier-Schellersheim M, Fowell DJ. "Inflammation-induced interstitial migration of effector CD4? T cells is dependent on integrin ?V." Nature immunology. 2013 Sep 0; 14(9):949-58. Epub 2013 Aug 11.
Batchu SN, Hughson A, Gerloff J, Fowell DJ, Korshunov VA. "Role of Axl in early kidney inflammation and progression of salt-dependent hypertension." Hypertension. 2013 Aug 0; 62(2):302-9. Epub 2013 Jun 17.
Lazarski CA, Ford J, Katzman SD, Rosenberg AF, Fowell DJ. "IL-4 attenuates Th1-associated chemokine expression and Th1 trafficking to inflamed tissues and limits pathogen clearance." PloS one. 2013 8(8):e71949. Epub 2013 Aug 26.
Hyun YM, Sumagin R, Sarangi PP, Lomakina E, Overstreet MG, Baker CM, Fowell DJ, Waugh RE, Sarelius IH, Kim M. "Uropod elongation is a common final step in leukocyte extravasation through inflamed vessels." The Journal of experimental medicine. 2012 Jul 2; 209(7):1349-62. Epub 2012 Jun 18.
Huang YH, Sojka DK, Fowell DJ. "Cutting edge: Regulatory T cells selectively attenuate, not terminate, T cell signaling by disrupting NF-?B nuclear accumulation in CD4 T cells." The Journal of immunology: Official journal of the American Association of Immunologists. 2012 Feb 1; 188(3):947-51. Epub 2012 Jan 06.
Mock DJ, Hollenbaugh JA, Daddacha W, Overstreet MG, Lazarski CA, Fowell DJ, Kim B. "Leishmania induces survival, proliferation and elevated cellular dNTP levels in human monocytes promoting acceleration of HIV co-infection." PLoS pathogens. 2012 8(4):e1002635. Epub 2012 Apr 05.
Sojka DK, Fowell DJ. "Regulatory T cells inhibit acute IFN-? synthesis without blocking T-helper cell type 1 (Th1) differentiation via a compartmentalized requirement for IL-10." Proceedings of the National Academy of Sciences of the United States of America. 2011 Nov 8; 108(45):18336-41. Epub 2011 Oct 24.
Singleton KL, Gosh M, Dandekar RD, Au-Yeung BB, Ksionda O, Tybulewicz VL, Altman A, Fowell DJ, Wülfing C. "Itk controls the spatiotemporal organization of T cell activation." Science signaling. 2011 Oct 4; 4(193):ra66.
Hughson A, Bromberg I, Johnson B, Quataert S, Jospe N, Fowell DJ. "Uncoupling of proliferation and cytokines from suppression within the CD4+CD25+Foxp3+ T-cell compartment in the 1st year of human type 1 diabetes." Diabetes. 2011 Aug 0; 60(8):2125-33. Epub 2011 Jun 29.
Sahu N, Morales JL, Fowell D, August A. "Modeling susceptibility versus resistance in allergic airway disease reveals regulation by Tec kinase Itk." PloS one. 2010 Jun 28; 5(6):e11348. Epub 2010 Jun 28.
Morales-Tirado V, Sojka DK, Katzman SD, Lazarski CA, Finkelman FD, Urban JF, Fowell DJ. "Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function." Blood. 2010 Apr 29; 115(17):3498-507. Epub 2009 Dec 23.
Sojka DK, Lazarski CA, Huang YH, Bromberg I, Hughson A, Fowell DJ. "Regulation of immunity at tissue sites of inflammation." Immunologic research. 2009 Dec 0; 45(2-3):239-50. Epub 2009 Jan 31.
Sojka DK, Hughson A, Fowell DJ. "CTLA-4 is required by CD4+CD25+ Treg to control CD4+ T-cell lymphopenia-induced proliferation." European journal of immunology. 2009 Jun 0; 39(6):1544-51.
Fowell DJ. "Signals for the execution of Th2 effector function." Cytokine. 2009 Apr 0; 46(1):1-6. Epub 2009 Feb 23.
Lazarski CA, Hughson A, Sojka DK, Fowell DJ. "Regulating Treg cells at sites of inflammation." Immunity. 2008 Oct 17; 29(4):511; author reply 512.
Sojka DK, Huang YH, Fowell DJ. "Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target." Immunology. 2008 May 0; 124(1):13-22. Epub 2008 Mar 14.
Katzman SD, Fowell DJ. "Pathogen-imposed skewing of mouse chemokine and cytokine expression at the infected tissue site." The Journal of clinical investigation. 2008 Feb 0; 118(2):801-11.
Zhao X, Zheng B, Huang Y, Yang D, Katzman S, Chang C, Fowell D, Zeng WP. "Interaction between GATA-3 and the transcriptional coregulator Pias1 is important for the regulation of Th2 immune responses." The Journal of immunology : official journal of the American Association of Immunologists. 2007 Dec 15; 179(12):8297-304.
Au-Yeung BB, Fowell DJ. "A key role for Itk in both IFN gamma and IL-4 production by NKT cells." The Journal of immunology: Official journal of the American Association of Immunologists. 2007 Jul 1; 179(1):111-9.
Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR. "T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5'-adenosine monophosphate to adenosine." The Journal of immunology: Official journal of the American Association of Immunologists. 2006 Nov 15; 177(10):6780-6.
Sukiennicki TL, Fowell DJ. "Distinct molecular program imposed on CD4+ T cell targets by CD4+CD25+ regulatory T cells." The Journal of immunology: Official journal of the American Association of Immunologists. 2006 Nov 15; 177(10):6952-61.
Au-Yeung BB, Katzman SD, Fowell DJ. "Cutting edge: Itk-dependent signals required for CD4+ T cells to exert, but not gain, Th2 effector function." The Journal of immunology: Official journal of the American Association of Immunologists. 2006 Apr 1; 176(7):3895-9.
Sojka DK, Hughson A, Sukiennicki TL, Fowell DJ. "Early kinetic window of target T cell susceptibility to CD25+ regulatory T cell activity." The Journal of immunology: Official journal of the American Association of Immunologists. 2005 Dec 1; 175(11):7274-80.
Morales-Tirado V, Johannson S, Hanson E, Howell A, Zhang J, Siminovitch KA, Fowell DJ. "Cutting edge: selective requirement for the Wiskott-Aldrich syndrome protein in cytokine, but not chemokine, secretion by CD4+ T cells." The Journal of immunology: Official journal of the American Association of Immunologists. 2004 Jul 15; 173(2):726-30.
Gurunathan S, Stobie L, Prussin C, Sacks DL, Glaichenhaus N, Iwasaki A, Fowell DJ, Locksley RM, Chang JT, Wu CY, Seder RA. "Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination: a potential immunoregulatory role for CD8+ T cells." The Journal of immunology: Official journal of the American Association of Immunologists. 2000 Jul 15; 165(2):915-24.
Pippig SD, Peña-Rossi C, Long J, Godfrey WR, Fowell DJ, Reiner SL, Birkeland ML, Locksley RM, Barclay AN, Killeen N. "Robust B cell immunity but impaired T cell proliferation in the absence of CD134 (OX40)." The Journal of immunology: Official journal of the American Association of Immunologists. 1999 Dec 15; 163(12):6520-9.
Heath VL, Hutchings P, Fowell DJ, Cooke A, Mason DW. "Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducing epitopes are different: evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes." Diabetes. 1999 Nov 0; 48(11):2157-65.
Fowell DJ, Shinkai K, Liao XC, Beebe AM, Coffman RL, Littman DR, Locksley RM. "Impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells." Immunity. 1999 Oct 0; 11(4):399-409.
Fowell DJ, Locksley RM. "Leishmania major infection of inbred mice: unmasking genetic determinants of infectious diseases." BioEssays : news and reviews in molecular, cellular and developmental biology. 1999 Jun 0; 21(6):510-8.
Pingel S, Launois P, Fowell DJ, Turck CW, Southwood S, Sette A, Glaichenhaus N, Louis JA, Locksley RM. "Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope." The Journal of experimental medicine. 1999 Apr 5; 189(7):1111-20.
Locksley RM, Pingel S, Lacy D, Wakil AE, Bix M, Fowell DJ. "Susceptibility to infectious diseases: Leishmania as a paradigm." The Journal of infectious diseases. 1999 Mar 0; 179 Suppl 2:S305-8.
Wakil AE, Wang ZE, Ryan JC, Fowell DJ, Locksley RM. "Interferon gamma derived from CD4(+) T cells is sufficient to mediate T helper cell type 1 development." The Journal of experimental medicine. 1998 Nov 2; 188(9):1651-6.
Fowell DJ, Bix M, Shinkai K, Lacy D, Locksley RM. "Disease susceptibility and development of the cytokine repertoire in the murine Leishmania major model." European cytokine network. 1998 Sep 0; 9(3 Suppl):102-6.
Reiner SL, Fowell DJ, Moskowitz NH, Swier K, Brown DR, Brown CR, Turck CW, Scott PA, Killeen N, Locksley RM. "Control of Leishmania major by a monoclonal alpha beta T cell repertoire." The Journal of immunology: Official journal of the American Association of Immunologists. 1998 Jan 15; 160(2):884-9.
Locksley RM, Fowell DJ, Shinkai K, Wakil AE, Lacy D, Bix M. "Development of CD4+ effector T cells and susceptibility to infectious diseases." Advances in experimental medicine and biology. 1998 452:45-52.
Hagenbaugh A, Sharma S, Dubinett SM, Wei SH, Aranda R, Cheroutre H, Fowell DJ, Binder S, Tsao B, Locksley RM, Moore KW, Kronenberg M. "Altered immune responses in interleukin 10 transgenic mice." The Journal of experimental medicine. 1997 Jun 16; 185(12):2101-10.
Fowell DJ, Magram J, Turck CW, Killeen N, Locksley RM. "Impaired Th2 subset development in the absence of CD4." Immunity. 1997 May 0; 6(5):559-69.
Saoudi A, Seddon B, Fowell D, Mason D. "The thymus contains a high frequency of cells that prevent autoimmune diabetes on transfer into prediabetic recipients." The Journal of experimental medicine. 1996 Dec 1; 184(6):2393-8.
Brown DR, Fowell DJ, Corry DB, Wynn TA, Moskowitz NH, Cheever AW, Locksley RM, Reiner SL. "Beta 2-microglobulin-dependent NK1.1+ T cells are not essential for T helper cell 2 immune responses." The Journal of experimental medicine. 1996 Oct 1; 184(4):1295-304.
Ramírez F, Fowell DJ, Puklavec M, Simmonds S, Mason D. "Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro." The Journal of immunology: Official journal of the American Association of Immunologists. 1996 Apr 1; 156(7):2406-12.
Heath VL, Saoudi A, Seddon BP, Moore NC, Fowell DJ, Mason DW. "The role of the thymus in the control of autoimmunity." Journal of autoimmunity. 1996 Apr 0; 9(2):241-6.
Saoudi A, Seddon B, Heath V, Fowell D, Mason D. "The physiological role of regulatory T cells in the prevention of autoimmunity: the function of the thymus in the generation of the regulatory T cell subset." Immunological reviews. 1996 Feb 0; 149:195-216.
Locksley RM, Wakil AE, Corry DB, Pingel S, Bix M, Fowell DJ. "The development of effector T cell subsets in murine Leishmania major infection." Ciba Foundation symposium. 1995 195:110-7; discussion 117-22.
Fowell D, Powrie F, Saoudi A, Seddon B, Heath V, Mason D. "The role of subsets of CD4+ T cells in autoimmunity." Ciba Foundation symposium. 1995 195:173-82; discussion 182-8.
Fowell DJ, Wakil AE, Locksley RM. "Interleukin-12 in murine leishmaniasis--match, flame or fuel?" Research in immunology. 1995 146(7-8):566-75.
Cyster JG, Fowell D, Barclay AN. "Antigenic determinants encoded by alternatively spliced exons of CD45 are determined by the polypeptide but influenced by glycosylation." International immunology. 1994 Dec 0; 6(12):1875-81.
Fowell D, Mason D. "Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential." The Journal of experimental medicine. 1993 Mar 1; 177(3):627-36.
Mason D, Fowell D. "T-cell subsets in autoimmunity." Current opinion in immunology. 1992 Dec 0; 4(6):728-32.
Fowell D, McKnight AJ, Powrie F, Dyke R, Mason D. "Subsets of CD4+ T cells and their roles in the induction and prevention of autoimmunity." Immunological reviews. 1991 Oct 0; 123:37-64.
Powrie F, Fowell D, McKnight AJ, Mason D. "Lineage relationships and functions of CD4+ T-cell subsets in the rat." Research in immunology. 1991 Jan 0; 142(1):54-8.
CD4 T Cell Motility in Inflamed Tissues
Cell migration is determined by the cell-intrinsic machinery for motility such as integrins, actin regulators and chemokine receptors and by the extrinsic composition of the extracellular matrix. The way in which effector CD4 T cells navigate through inflamed interstitial tissue at sites of infection is not well understood.
Spatiotemporal Control of Effector Function in Infected Tissues
The molecular control of CD4 differentiation into functionally distinct effector lineages has been extensively studied but the fate of the effector T cells once they leave the lymph node is less well understood. We are interested in how the inflammatory milieu at sites of infection and autoimmune attack may modify the effector function of CD4+ T cells.
Perivascular Activation Niches
Despite a random pattern of T cell migration in the lymph node and peripheral tissues, T cell activation shows a high degree of spatial preference. We have identified a perivascular activation niche in the inflamed skin that links Th1 tissue entry with early activation.
Tfh Control of the Germinal Center Response
Key to successful vaccination is the development of high affinity antibody production. T follicular helper (Tfh) cells play an essential role in regulating B cell affinity maturation in the germinal center of the lymph node. We are interested in the spatial cues that regulate Tfh germinal center retention and in understanding the temporal requirements for Tfh support of long-lived plasma cell generation.