Analysis of therapeutic potential of preclinical models based on DR3/TL1A pathway modulation (Review)

Dostert C, Grusdat M, Letellier E and Brenner D: The TNF Family of Ligands and Receptors: Communication Modules in the Immune System and Beyond. Physiol Rev. 99:115–160. 2019.PubMed/NCBI View Article : Google Scholar

Aggarwal BB, Gupta SC and Kim JH: Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 119:651–665. 2012.PubMed/NCBI View Article : Google Scholar

Yang Y, Yeh SH, Madireddi S, Matochko WL, Gu C, Pacheco Sanchez P, Ultsch M, De Leon Boenig G, Harris SF, Leonard B, et al: Tetravalent biepitopic targeting enables intrinsic antibody agonism of tumor necrosis factor receptor superfamily members. MAbs. 11:996–1011. 2019.PubMed/NCBI View Article : Google Scholar

Valatas V, Kolios G and Bamias G: TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity. Front Immunol. 10(583)2019.PubMed/NCBI View Article : Google Scholar

Li L, Fu L, Zhou P, Lu Y, Zhang L, Wang W, Nie J, Zhang D, Liu Y, Wu B, et al: Effects of tumor necrosis factor-like ligand 1A (TL1A) on imiquimod-induced psoriasiform skin inflammation in mice. Arch Dermatol Res. 312:481–490. 2020.PubMed/NCBI View Article : Google Scholar

Clarke AW, Poulton L, Shim D, Mabon D, Butt D, Pollard M, Pande V, Husten J, Lyons J, Tian C, et al: An anti-TL1A antibody for the treatment of asthma and inflammatory bowel disease. MAbs. 10:664–677. 2018.PubMed/NCBI View Article : Google Scholar

Richard AC, Tan C, Hawley ET, Gomez-Rodriguez J, Goswami R, Yang XP, Cruz AC, Penumetcha P, Hayes ET, Pelletier M, et al: The TNF-family ligand TL1A and its receptor DR3 promote T cell-mediated allergic immunopathology by enhancing differentiation and pathogenicity of IL-9-producing T cells. J Immunol. 194:3567–3582. 2015.PubMed/NCBI View Article : Google Scholar

Schreiber TH, Wolf D, Tsai MS, Chirinos J, Deyev VV, Gonzalez L, Malek TR, Levy RB and Podack ER: Therapeutic Treg expansion in mice by TNFRSF25 prevents allergic lung inflammation. J Clin Invest. 120:3629–3640. 2010.PubMed/NCBI View Article : Google Scholar

Khan SQ, Tsai MS, Schreiber TH, Wolf D, Deyev VV and Podack ER: Cloning, expression, and functional characterization of TL1A-Ig. J Immunol. 190:1540–1550. 2013.PubMed/NCBI View Article : Google Scholar

Mavers M, Simonetta F, Nishikii H, Ribado JV, Maas-Bauer K, Alvarez M, Hirai T, Turkoz M, Baker J and Negrin RS: Activation of the DR3-TL1A Axis in Donor Mice Leads to Regulatory T Cell Expansion and Activation With Reduction in Graft-Versus-Host Disease. Front Immunol. 10(1624)2019.PubMed/NCBI View Article : Google Scholar

Chinnaiyan AM, O'Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, Xing L, Gentz R, Ni J and Dixit VM: Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science. 274:990–992. 1996.PubMed/NCBI View Article : Google Scholar

Perks WV, Singh RK, Jones GW, Twohig JP, Williams AS, Humphreys IR, Taylor PR, Jones SA and Wang ECY: Death Receptor 3 Promotes Chemokine-Directed Leukocyte Recruitment in Acute Resolving Inflammation and Is Essential for Pathological Development of Mesothelial Fibrosis in Chronic Disease. Am J Pathol. 186:2813–2823. 2016.PubMed/NCBI View Article : Google Scholar

Wang EC, Kitson J, Thern A, Williamson J, Farrow SN and Owen MJ: Genomic structure, expression, and chromosome mapping of the mouse homologue for the WSL-1 (DR3, Apo3, TRAMP, LARD, TR3, TNFRSF12) gene. Immunogenetics. 53:59–63. 2001.PubMed/NCBI View Article : Google Scholar

Screaton GR, Xu XN, Olsen AL, Cowper AE, Tan R, McMichael AJ and Bell JI: LARD: A new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing. Proc Natl Acad Sci USA. 94:4615–4619. 1997.PubMed/NCBI View Article : Google Scholar

Schreiber TH and Podack ER: Immunobiology of TNFSF15 and TNFRSF25. Immunol Res. 57:3–11. 2013.PubMed/NCBI View Article : Google Scholar

Gout S, Morin C, Houle F and Huot J: Death receptor-3, a new E-Selectin counter-receptor that confers migration and survival advantages to colon carcinoma cells by triggering p38 and ERK MAPK activation. Cancer Res. 66:9117–9124. 2006.PubMed/NCBI View Article : Google Scholar

Al-Lamki RS, Wang J, Thiru S, Pritchard NR, Bradley JA, Pober JS and Bradley JR: Expression of silencer of death domains and death-receptor-3 in normal human kidney and in rejecting renal transplants. Am J Pathol. 163:401–411. 2003.PubMed/NCBI View Article : Google Scholar

Liu W, Vetreno RP and Crews FT: Hippocampal TNF-death receptors, caspase cell death cascades, and IL-8 in alcohol use disorder. Mol Psychiatry: Mar 5, 2020 (Epub ahead of print). doi: 10.1038/s41380-020-0698-4.

Bittner S and Ehrenschwender M: Multifaceted death receptor 3 signaling-promoting survival and triggering death. FEBS Lett. 591:2543–2555. 2017.PubMed/NCBI View Article : Google Scholar

Collins FL, Stone MD, Turton J, McCabe LR, Wang ECY and Williams AS: Oestrogen-deficiency induces bone loss by modulating CD14⁺ monocyte and CD4⁺ T cell DR3 expression and serum TL1A levels. BMC Musculoskelet Disord. 20(326)2019.PubMed/NCBI View Article : Google Scholar

Della Bella S, Calcaterra F, Bacci M, Carenza C, Pandolfo C, Ferrazzi P, Uva P, Pagani M, Lodigiani C and Mavilio D: Pathologic up-regulation of TNFSF15-TNFRSF25 axis sustains endothelial dysfunction in unprovoked venous thromboembolism. Cardiovasc Res. 116:698–707. 2020.PubMed/NCBI View Article : Google Scholar

Slebioda TJ, Bojarska-Junak A, Cyman M, Landowski P, Kaminska B, Celinski K and Kmiec Z: Expression of death receptor 3 on peripheral blood mononuclear cells differes in adult IBD patients and children with newly diagnosed IBD. Cytometry B Clin Cytom. 92:165–169. 2017.PubMed/NCBI View Article : Google Scholar

Facco M, Cabrelle A, Calabrese F, Teramo A, Cinetto F, Carraro S, Martini V, Calzetti F, Tamassia N, Cassatella MA, et al: TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis. Clin Mol Allergy. 13(16)2015.PubMed/NCBI View Article : Google Scholar

Li L, Lu Y, Fu L, Zhou P, Zhang L, Wang W, Nie J, Zhang D, Liu Y, Wu B, et al: Expression of death receptor 3 (DR3) on peripheral blood mononuclear cells of patients with psoriasis vulgaris. Postgrad Med J. 94:551–555. 2018.PubMed/NCBI View Article : Google Scholar

Safaya S, Alfarhan M, Sulaiman A, Alsulaiman A and Al-Ali A: TNFSF/TNFRSF cytokine gene expression in sickle cell anemia: Up-regulated TNF-like cytokine 1A (TL1A) and its decoy receptor (DcR3) in peripheral blood mononuclear cells and plasma. Cytokine. 123(154744)2019.PubMed/NCBI View Article : Google Scholar

Ślebioda TJ, Stanisławowski M, Cyman M, Wierzbicki PM, Żurawa-Janicka D, Kobiela J, Makarewicz W, Guzek M and Kmieć Z: Distinct Expression Patterns of Two Tumor Necrosis Factor Superfamily Member 15 Gene Isoforms in Human Colon Cancer. Dig Dis Sci. 64:1857–1867. 2019.PubMed/NCBI View Article : Google Scholar

Bittner S, Knoll G, Füllsack S, Kurz M, Wajant H and Ehrenschwender M: Soluble TL1A is sufficient for activation of death receptor 3. FEBS J. 283:323–336. 2016.PubMed/NCBI View Article : Google Scholar

Li Z, Buttó LF, Buela KA, Jia LG, Lam M, Ward JD, Pizarro TT and Cominelli F: Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn's Disease-Like Ileitis. Front Immunol. 9(362)2018.PubMed/NCBI View Article : Google Scholar

Nishikii H, Kim BS, Yokoyama Y, Chen Y, Baker J, Pierini A, Alvarez M, Mavers M, Maas-Bauer K, Pan Y, et al: DR3 signaling modulates the function of Foxp3⁺ regulatory T cells and the severity of acute graft-versus-host disease. Blood. 128:2846–2858. 2016.PubMed/NCBI View Article : Google Scholar

Xu LX, Grimaldo S, Qi JW, Yang GL, Qin TT, Xiao HY, Xiang R, Xiao Z, Li LY and Zhang ZS: Death receptor 3 mediates TNFSF15- and TNFα-induced endothelial cell apoptosis. Int J Biochem Cell Biol. 55:109–118. 2014.PubMed/NCBI View Article : Google Scholar

Buttó LF, Jia LG, Arseneau KO, Tamagawa H, Rodriguez-Palacios A, Li Z, De Salvo C, Pizarro TT, Bamias G and Cominelli F: Death-Domain-Receptor 3 Deletion Normalizes Inflammatory Gene Expression and Prevents Ileitis in Experimental Crohn's Disease. Inflamm Bowel Dis. 25:14–26. 2019.PubMed/NCBI View Article : Google Scholar

Li J, Shi W, Sun H, Ji Y, Chen Y, Guo X, Sheng H, Shu J, Zhou L, Cai T, et al: Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation. Nat Commun. 10(3371)2019.PubMed/NCBI View Article : Google Scholar

Castellanos JG, Woo V, Viladomiu M, Putzel G, Lima S, Diehl GE, Marderstein AR, Gandara J, Perez AR, Withers DR, et al: Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis. Immunity. 49:1077–1089.e5. 2018.PubMed/NCBI View Article : Google Scholar

Karta MR, Broide DH and Doherty TA: Insights into Group 2 Innate Lymphoid Cells in Human Airway Disease. Curr Allergy Asthma Rep. 16(8)2016.PubMed/NCBI View Article : Google Scholar

Singh RK, Perks WV, Twohig JP, Kidd EJ, Broadley K, Farrow SN, Williams AS, Taylor PR and Wang ECY: Death Receptor 3 regulates distinct pathological attributes of acute versus chronic murine allergic lung inflammation. Cell Immunol. 320:62–70. 2017.PubMed/NCBI View Article : Google Scholar

Jin S, Chin J, Seeber S, Niewoehner J, Weiser B, Beaucamp N, Woods J, Murphy C, Fanning A, Shanahan F, et al: TL1A/TNFSF15 directly induces proinflammatory cytokines, including TNFα, from CD3⁺CD161⁺ T cells to exacerbate gut inflammation. Mucosal Immunol. 6:886–899. 2013.PubMed/NCBI View Article : Google Scholar

Papadakis KA, Zhu D, Prehn JL, Landers C, Avanesyan A, Lafkas G and Targan SR: Dominant role for TL1A/DR3 pathway in IL-12 plus IL-18-induced IFN-gamma production by peripheral blood and mucosal CCR9⁺ T lymphocytes. J Immunol. 174:4985–4990. 2005.PubMed/NCBI View Article : Google Scholar

Siakavellas SI and Bamias G: Tumor Necrosis Factor-like Cytokine TL1A and Its Receptors DR3 and DcR3: Important New Factors in Mucosal Homeostasis and Inflammation. Inflamm Bowel Dis. 21:2441–2452. 2015.PubMed/NCBI View Article : Google Scholar

Fang L, Adkins B, Deyev V and Podack ER: Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation. J Exp Med. 205:1037–1048. 2008.PubMed/NCBI View Article : Google Scholar

Meylan F, Davidson TS, Kahle E, Kinder M, Acharya K, Jankovic D, Bundoc V, Hodges M, Shevach EM, Keane-Myers A, et al: The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases. Immunity. 29:79–89. 2008.PubMed/NCBI View Article : Google Scholar

Basnyat P, Sumelahti ML, Lehtimäki T, Elovaara I and Hagman S: Gene expression profiles of TNF-like cytokine 1A (TL1A) and its receptors death receptor 3 (DR3) and decoy receptor 3 (DcR3) in multiple sclerosis. J Neuroimmunol. 335(577020)2019.PubMed/NCBI View Article : Google Scholar

Jones GW, Stumhofer JS, Foster T, Twohig JP, Hertzog P, Topley N, Williams AS, Hunter CA, Jenkins BJ, Wang EC, et al: Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation. FASEB J. 25:409–419. 2011.PubMed/NCBI View Article : Google Scholar

Zhou M, Liu R, Su D, Feng X and Li X: TL1A increased the differentiation of peripheral Th17 in rheumatoid arthritis. Cytokine. 69:125–130. 2014.PubMed/NCBI View Article : Google Scholar

Pappu BP, Borodovsky A, Zheng TS, Yang X, Wu P, Dong X, Weng S, Browning B, Scott ML, Ma L, et al: TL1A-DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease. J Exp Med. 205:1049–1062. 2008.PubMed/NCBI View Article : Google Scholar

Wang D, Li H, Duan YY, Han F, Luo YX, Wu MY, Yang MY, Zhan RR, Song J, Zhang H, et al: TL1A modulates the severity of colitis by promoting Th9 differentiation and IL-9 secretion. Life Sci. 231(116536)2019.PubMed/NCBI View Article : Google Scholar

Tsuda M, Hamade H, Thomas LS, Salumbides BC, Potdar AA, Wong MH, Nunnelee JS, Stamps JT, Neutzsky-Wulff AV, Barrett RJ, et al: A role for BATF3 in TH9 differentiation and T-cell-driven mucosal pathologies. Mucosal Immunol. 12:644–655. 2019.PubMed/NCBI View Article : Google Scholar

Meylan F, Hawley ET, Barron L, Barlow JL, Penumetcha P, Pelletier M, Sciumè G, Richard AC, Hayes ET, Gomez-Rodriguez J, et al: The TNF-family cytokine TL1A promotes allergic immunopathology through group 2 innate lymphoid cells. Mucosal Immunol. 7:958–968. 2014.PubMed/NCBI View Article : Google Scholar

Castellanos JG and Longman RS: Innate lymphoid cells link gut microbes with mucosal T cell immunity. Gut Microbes. 11:231–236. 2020.PubMed/NCBI View Article : Google Scholar

Bull MJ, Williams AS, Mecklenburgh Z, Calder CJ, Twohig JP, Elford C, Evans BA, Rowley TF, Slebioda TJ, Taraban VY, et al: The Death Receptor 3-TNF-like protein 1A pathway drives adverse bone pathology in inflammatory arthritis. J Exp Med. 205:2457–2464. 2008.PubMed/NCBI View Article : Google Scholar

Tougaard P, Zervides KA, Skov S, Hansen AK and Pedersen AE: Biologics beyond TNF-α inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders. Immunopharmacol Immunotoxicol. 38:29–38. 2016.PubMed/NCBI View Article : Google Scholar

Takedatsu H, Michelsen KS, Wei B, Landers CJ, Thomas LS, Dhall D, Braun J and Targan SR: TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology. 135:552–567. 2008.PubMed/NCBI View Article : Google Scholar

Meylan F, Song YJ, Fuss I, Villarreal S, Kahle E, Malm IJ, Acharya K, Ramos HL, Lo L, Mentink-Kane MM, et al: The TNF-family cytokine TL1A drives IL-13-dependent small intestinal inflammation. Mucosal Immunol. 4:172–185. 2011.PubMed/NCBI View Article : Google Scholar

Shih DQ, Zheng L, Zhang X, Zhang H, Kanazawa Y, Ichikawa R, Wallace KL, Chen J, Pothoulakis C, Koon HW, et al: Inhibition of a novel fibrogenic factor Tl1a reverses established colonic fibrosis. Mucosal Immunol. 7:1492–1503. 2014.PubMed/NCBI View Article : Google Scholar

Li H, Song J, Niu G, Zhang H, Guo J, Shih DQ, Targan SR and Zhang X: TL1A blocking ameliorates intestinal fibrosis in the T cell transfer model of chronic colitis in mice. Pathol Res Pract. 214:217–227. 2018.PubMed/NCBI View Article : Google Scholar

Deng G, Song X and Greene MI: FoxP3 in Treg cell biology: A molecular and structural perspective. Clin Exp Immunol. 199:255–262. 2020.PubMed/NCBI View Article : Google Scholar

Williams LM and Rudensky AY: Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol. 8:277–284. 2007.PubMed/NCBI View Article : Google Scholar

Allos H, Al Dulaijan BS, Choi J and Azzi J: Regulatory T Cells for More Targeted Immunosuppressive Therapies. Clin Lab Med. 39:1–13. 2019.PubMed/NCBI View Article : Google Scholar

Lubrano di Ricco M, Ronin E, Collares D, Divoux J, Grégoire S, Wajant H, Gomes T, Grinberg-Bleyer Y, Baud V, Marodon G, et al: Tumor necrosis factor receptor family costimulation increases regulatory T-cell activation and function via NF-κB. Eur J Immunol. 50:972–985. 2020.PubMed/NCBI View Article : Google Scholar

Bittner S, Knoll G and Ehrenschwender M: Death receptor 3 signaling enhances proliferation of human regulatory T cells. FEBS Lett. 591:1187–1195. 2017.PubMed/NCBI View Article : Google Scholar

Tran GT, Hodgkinson SJ, Carter N, Verma ND, Robinson CM, Plain KM, Nomura M and Hall BM: Autoantigen specific IL-2 activated CD4⁺CD25⁺T regulatory cells inhibit induction of experimental autoimmune neuritis. J Neuroimmunol. 341(577186)2020.PubMed/NCBI View Article : Google Scholar

Zhang J, Czerpaniak K, Huang L, Liu X, Cloud ME, Unsinger J, Hotchkiss RS, Li D and Cao YQ: Low-dose interleukin-2 reverses behavioral sensitization in multiple mouse models of headache disorders. Pain. 161:1381–1398. 2020.PubMed/NCBI View Article : Google Scholar

Scalapino KJ, Tang Q, Bluestone JA, Bonyhadi ML and Daikh DI: Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells. J Immunol. 177:1451–1459. 2006.PubMed/NCBI View Article : Google Scholar

Canavan JB, Scottà C, Vossenkämper A, Goldberg R, Elder MJ, Shoval I, Marks E, Stolarczyk E, Lo JW, Powell N, et al: Developing in vitro expanded CD45RA⁺ regulatory T cells as an adoptive cell therapy for Crohn's disease. Gut. 65:584–594. 2016.PubMed/NCBI View Article : Google Scholar

Golshayan D, Jiang S, Tsang J, Garin MI, Mottet C and Lechler RI: In vitro-expanded donor alloantigen-specific CD4⁺CD25⁺ regulatory T cells promote experimental transplantation tolerance. Blood. 109:827–835. 2007.PubMed/NCBI View Article : Google Scholar

Xia G, He J and Leventhal JR: Ex vivo-expanded natural CD4⁺CD25⁺ regulatory T cells synergize with host T-cell depletion to promote long-term survival of allografts. Am J Transplant. 8:298–306. 2008.PubMed/NCBI View Article : Google Scholar

Matsuoka KI: Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: Current understanding and future perspectives. Int J Hematol. 107:130–137. 2018.PubMed/NCBI View Article : Google Scholar

Kapur R, Kim M, Aslam R, McVey MJ, Tabuchi A, Luo A, Liu J, Li Y, Shanmugabhavananthan S, Speck ER, et al: T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10. Blood. 129:2557–2569. 2017.PubMed/NCBI View Article : Google Scholar

He R, Li L, Kong Y, Tian L, Tian X, Fang P, Bian M and Liu Z: Preventing murine transfusion-related acute lung injury by expansion of CD4⁺ CD25⁺ FoxP3⁺ Tregs using IL-2/anti-IL-2 complexes. Transfusion. 59:534–544. 2019.PubMed/NCBI View Article : Google Scholar

Madireddi S, Eun SY, Mehta AK, Birta A, Zajonc DM, Niki T, Hirashima M, Podack ER, Schreiber TH and Croft M: Regulatory T Cell-Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9. J Immunol. 199:2721–2728. 2017.PubMed/NCBI View Article : Google Scholar

Schreiber TH, Wolf D, Bodero M, Gonzalez L and Podack ER: T cell costimulation by TNFR superfamily (TNFRSF)4 and TNFRSF25 in the context of vaccination. J Immunol. 189:3311–3318. 2012.PubMed/NCBI View Article : Google Scholar

Wolf D, Schreiber TH, Tryphonopoulos P, Li S, Tzakis AG, Ruiz P and Podack ER: Tregs expanded in vivo by TNFRSF25 agonists promote cardiac allograft survival. Transplantation. 94:569–574. 2012.PubMed/NCBI View Article : Google Scholar

Wolf D, Bader CS, Barreras H, Copsel S, Pfeiffer BJ, Lightbourn CO, Altman NH, Komanduri KV and Levy RB: Superior immune reconstitution using Treg-expanded donor cells versus PTCy treatment in preclinical HSCT models. JCI Insight. 3(e121717)2018.PubMed/NCBI View Article : Google Scholar

Gorczynski RM, Sadozai H, Zhu F and Khatri I: Effect of infusion of monoclonal antibodies to tumour necrosis factor-receptor super family 25 on graft rejection in allo-immune mice receiving autologous marrow transplantation. Immunology. 150:418–431. 2017.PubMed/NCBI View Article : Google Scholar

Pierini A, Colonna L, Alvarez M, Schneidawind D, Nishikii H, Baker J, Pan Y, Florek M, Kim BS and Negrin RS: Donor Requirements for Regulatory T Cell Suppression of Murine Graft-versus-Host Disease. J Immunol. 195:347–355. 2015.PubMed/NCBI View Article : Google Scholar

Hoffmann P, Ermann J, Edinger M, Fathman CG and Strober S: Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 196:389–399. 2002.PubMed/NCBI View Article : Google Scholar

Kim BS, Nishikii H, Baker J, Pierini A, Schneidawind D, Pan Y, Beilhack A, Park CG and Negrin RS: Treatment with agonistic DR3 antibody results in expansion of donor Tregs and reduced graft-versus-host disease. Blood. 126:546–557. 2015.PubMed/NCBI View Article : Google Scholar

Wolf D, Barreras H, Bader CS, Copsel S, Lightbourn CO, Pfeiffer BJ, Altman NH, Podack ER, Komanduri KV and Levy RB: Marked In Vivo Donor Regulatory T Cell Expansion via Interleukin-2 and TL1A-Ig Stimulation Ameliorates Graft-versus-Host Disease but Preserves Graft-versus-Leukemia in Recipients after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 23:757–766. 2017.PubMed/NCBI View Article : Google Scholar

Copsel S, Wolf D, Kale B, Barreras H, Lightbourn CO, Bader CS, Alperstein W, Altman NH, Komanduri KV and Levy RB: Very Low Numbers of CD4⁺ FoxP3⁺ Tregs Expanded in Donors via TL1A-Ig and Low-Dose IL-2 Exhibit a Distinct Activation/Functional Profile and Suppress GVHD in a Preclinical Model. Biol Blood Marrow Transplant. 24:1788–1794. 2018.PubMed/NCBI View Article : Google Scholar