Danyvid Olivares-Villagomez, Ph.D.

Research Associate Professor

Faculty Appointments
Research Associate Professor of Pathology, Microbiology and Immunology
Ph.D., PATHOLOGY, New York University, New York, New YorkM.S., Biology , Vanderbilt University, Nashville, TennesseeB.S., Universidad Nacional Autónoma de México, Mexico City, Mexico
Office Address
21 Ave and Garland, 811 Light Hall. Nashville TN 37232
Research Description
Our bodies are constantly exposed to infectious agents wanting to invade and cause harm. One of the areas with high exposure to foreign antigens is the mucosa of the digestive tract. The mucosal immune system protects the intestines from pathogenic invaders and at the same time discriminates those organisms that are important for our overall homeostasis. My research focuses in the role of a molecule conspicuously expressed in the intestinal epithelial cells (IEC), known as thymus leukemia (TL) antigen, and its interaction with CD8alpha homodimers expressed by intestinal intraepithelial lymphocytes (IEL).

IEL are a group of lymphocytes that in the mouse are comprised primarily of TCRalpha-beta and TCRgamma-delta cells. The great majority of these cells express CD8alpha-alpha. It is thought that TL on IEC interacts and modulates the response of CD8alpha-alpha+ cells. To understand the role of the CD8alpha-alpha-TL interaction, we developed a mouse line that lacks expression of TL. We showed that IEL from TL-deficient mice proliferate more in vivo and in vitro, are more cytotoxic and produce larger amounts of IFN-gamma. Moreover, when TL-deficient mice were crossed with TCRalpha-deficient animals (a susceptible strain of mice for the development of IBD), we observed that TL-deficiency increases the severity and the onset of IBD. These results indicate that TL functions as a check point for the prevention of IBD.

My current research is trying to understand the molecular mechanisms governing the interaction of TL-CD8alpha-alpha, and how lymphocytes respond in the absence of these two molecules.

Research Keywords
Mucosal immunology
Olivares-Villagómez D, Algood HM, Singh K, Parekh VV, Ryan KE, Piazuelo MB, Wilson KT, Van Kaer L. Intestinal epithelial cells modulate CD4 T cell responses via the thymus leukemia antigen. J. Immunol [print-electronic]. 2011 Oct 10/15/2011; 187(8): 4051-60. PMID: 21900182, PMCID: PMC3186831, PII: jimmunol.1101052, DOI: 10.4049/jimmunol.1101052, ISSN: 1550-6606.

Goettel JA, Scott Algood HM, Olivares-Villagómez D, Washington MK, Chaturvedi R, Wilson KT, Van Kaer L, Polk DB. KSR1 protects from interleukin-10 deficiency-induced colitis in mice by suppressing T-lymphocyte interferon-¿ production. Gastroenterology [print-electronic]. 2011 Jan; 140(1): 265-74. PMID: 20875416, PMCID: PMC3008308, PII: S0016-5085(10)01421-6, DOI: 10.1053/j.gastro.2010.09.041, ISSN: 1528-0012.

Olivares-Villagómez D, Van Kaer L. TL and CD8aa: Enigmatic partners in mucosal immunity. Immunol. Lett [print-electronic]. 2010 Nov 11/30/2010; 134(1): 1-6. PMID: 20850477, PMCID: PMC2967663, PII: S0165-2478(10)00224-5, DOI: 10.1016/j.imlet.2010.09.004, ISSN: 1879-0542.

Olivares-Villagómez D, Mendez-Fernandez YV, Parekh VV, Lalani S, Vincent TL, Cheroutre H, Van Kaer L. Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Nov 11/18/2008; 105(46): 17931-6. PMID: 19004778, PMCID: PMC2584730, PII: 0808242105, DOI: 10.1073/pnas.0808242105, ISSN: 1091-6490.

Yan J, Parekh VV, Mendez-Fernandez Y, Olivares-Villagómez D, Dragovic S, Hill T, Roopenian DC, Joyce S, Van Kaer L. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J. Exp. Med [print-electronic]. 2006 Mar 3/20/2006; 203(3): 647-59. PMID: 16505142, PMCID: PMC2118255, PII: jem.20052271, DOI: 10.1084/jem.20052271, ISSN: 0022-1007.

Shen S, Ding Y, Tadokoro CE, Olivares-Villagómez D, Camps-Ramírez M, Curotto de Lafaille MA, Lafaille JJ. Control of homeostatic proliferation by regulatory T cells. J. Clin. Invest [print-electronic]. 2005 Dec; 115(12): 3517-26. PMID: 16294223, PMCID: PMC1283941, DOI: 10.1172/JCI25463, ISSN: 0021-9738.

Parekh VV, Wilson MT, Olivares-Villagómez D, Singh AK, Wu L, Wang CR, Joyce S, Van Kaer L. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J. Clin. Invest. 2005 Sep; 115(9): 2572-83. PMID: 16138194, PMCID: PMC1193878, DOI: 10.1172/JCI24762, ISSN: 0021-9738.

Curotto de Lafaille MA, Shen S, Olivares-Villagómez D, Camps-Ramírez M, Lafaille JJ. Do regulatory T cells play a role in the control of homeostatic proliferation?. Int. Rev. Immunol. 2005 May; 24(3-4): 269-84. PMID: 16036378, PII: M107311R17237855, DOI: 10.1080/08830180590935001, ISSN: 0883-0185.

Parekh VV, Singh AK, Wilson MT, Olivares-Villagómez D, Bezbradica JS, Inazawa H, Ehara H, Sakai T, Serizawa I, Wu L, Wang CR, Joyce S, Van Kaer L. Quantitative and qualitative differences in the in vivo response of NKT cells to distinct alpha- and beta-anomeric glycolipids. J. Immunol. 2004 Sep 9/15/2004; 173(6): 3693-706. PMID: 15356115, PII: 173/6/3693, ISSN: 0022-1767.

Zhang J, Dong M, Li L, Fan Y, Pathre P, Dong J, Lou D, Wells JM, Olivares-Villagómez D, Van Kaer L, Wang X, Xu M. Endonuclease G is required for early embryogenesis and normal apoptosis in mice. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2003 Dec 12/23/2003; 100(26): 15782-7. PMID: 14663139, PMCID: PMC307645, PII: 2636393100, DOI: 10.1073/pnas.2636393100, ISSN: 0027-8424.

Wilson MT, Johansson C, Olivares-Villagómez D, Singh AK, Stanic AK, Wang CR, Joyce S, Wick MJ, Van Kaer L. The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2003 Sep 9/16/2003; 100(19): 10913-8. PMID: 12960397, PMCID: PMC196902, PII: 1833166100, DOI: 10.1073/pnas.1833166100, ISSN: 0027-8424.

Lane JE, Ribeiro-Rodrigues R, Olivares-Villagómez D, Vnencak-Jones CL, McCurley TL, Carter CE. Detection of Trypanosoma cruzi DNA within murine cardiac tissue sections by in situ polymerase chain reaction. Mem. Inst. Oswaldo Cruz [print-electronic]. 2003 Apr; 98(3): 373-6. PMID: 12886417, PII: S0074-02762003000300013, ISSN: 0074-0276.

Singh AK, Wilson MT, Hong S, Olivares-Villagómez D, Du C, Stanic AK, Joyce S, Sriram S, Koezuka Y, Van Kaer L. Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J. Exp. Med. 2001 Dec 12/17/2001; 194(12): 1801-11. PMID: 11748281, PMCID: PMC2193577, ISSN: 0022-1007.

Curotto de Lafaille MA, Muriglan S, Sunshine MJ, Lei Y, Kutchukhidze N, Furtado GC, Wensky AK, Olivares-Villagómez D, Lafaille JJ. Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes. J. Exp. Med. 2001 Nov 11/5/2001; 194(9): 1349-59. PMID: 11696599, PMCID: PMC2195981, ISSN: 0022-1007.

Furtado GC, Olivares-Villagómez D, Curotto de Lafaille MA, Wensky AK, Latkowski JA, Lafaille JJ. Regulatory T cells in spontaneous autoimmune encephalomyelitis. Immunol. Rev. 2001 Aug; 182: 122-34. PMID: 11722629, PII: 1820110, ISSN: 0105-2896.

Olivares-Villagómez D, Wensky AK, Wang Y, Lafaille JJ. Repertoire requirements of CD4+ T cells that prevent spontaneous autoimmune encephalomyelitis. J. Immunol. 2000 May 5/15/2000; 164(10): 5499-507. PMID: 10799918, PII: ji_v164n10p5499, ISSN: 0022-1767.

Olivares-Villagómez D, Wang Y, Lafaille JJ. Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis. J. Exp. Med. 1998 Nov 11/16/1998; 188(10): 1883-94. PMID: 9815266, PMCID: PMC2212402, ISSN: 0022-1007.

Olivares-Villagómez D, McCurley TL, Vnencak-Jones CL, Correa-Oliveira R, Colley DG, Carter CE. Polymerase chain reaction amplification of three different Trypanosoma cruzi DNA sequences from human chagasic cardiac tissue. Am. J. Trop. Med. Hyg. 1998 Oct; 59(4): 563-70. PMID: 9790431, ISSN: 0002-9637.

Lane JE, Olivares-Villagomez D, Vnencak-Jones CL, McCurley TL, Carter CE. Detection of Trypanosoma cruzi with the polymerase chain reaction and in situ hybridization in infected murine cardiac tissue. Am. J. Trop. Med. Hyg. 1997 Jun; 56(6): 588-95. PMID: 9230784, ISSN: 0002-9637.

Olivares-Villagómez, D., Algood, H.M., Parekh, V.V., Singh, K., Ryan, K., M. Blanca Piazuelo, Wilson, K.T., and Van Kaer, L. Intestinal epithelial cells modulate CD4 T cell responses via the thymus leukemia antigen. Journal of Immunology.

Huang, Y., Park, Y., Wang-Zhu, Y., Larange, A., Arens, R., Bernardol, I., Olivares-Villagómez, D., Herndler-Brandstetter, D., Abraham, N., Grubeck-Loebenstein, B., Schoenberger, S.P., Van Kaer, L., Kronenberg, M., Teitell, A., and Cheroutre, H. Mucosal CD8 memory T cells are selected in the periphery by an MHC class I molecule. Nature Immunology.