Selected Publications

Publications most relevant to the current research projects

Innate-like lymphocytes and their contribution to metabolic disease

1. Olivares-Villagomez, D., Mendez-Fernandez, Y., Parekh, V.V., Lalani, S., Vincent, T.L., Cheroutre, H., and Van Kaer, L. (2008). Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease. Proc. Natl. Acad. Sci. USA 105, 17931-17936.

2. Olivares-Villagómez, D., Algood, H.M., Singh, K., Parekh, V.V., Ryan, K., Piazuelo, M.B., Wilson, K.T., and Van Kaer, L. (2011). Intestinal epithelial cells modulate CD4 T cell responses via the thymus leukemia antigen. J. Immunol. 187, 4051-4060.

3. Wu, L., Parekh, V.V., Gabriel, C.L., Bracy, D.P., Marks-Shulman, P.A., Tamboli, R.A., Kim, S., Mendez-Fernandez, Y.V., Besra, G.S., Lomenick, J.P., Williams, B., Wasserman, D.H., and Van Kaer, L. (2012). Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance and hepatic steatosis in obese mice. Proc. Natl. Acad. Sci. USA 109, E1143-E1152.

4. Van Kaer, L., Parekh, V.V., and Wu, L. (2013). Review: iNKT cells as sensors and managers of inflammation. Trends Immunol. 34, 50-58.

5. Parekh, V.V., Wu, L., Olivares-Villagómez, D., Wilson, K.T., and Van Kaer, L. (2013). Activated invariant NKT cells control central nervous system autoimmunity in a mechanism that involves myeloid-derived suppressor cells. J. Immunol. 190, 1948-1960.

6. Van Kaer, L., Scott Algood, H.M., Singh, K., Parekh, V.V., Greer, M.J., Piazuelo, M.B., Weitkamp, J.-H., Matta, P., Chaturvedi, R., Wilson, K.T., and Olivares-Villagómez, D. (2014). CD8alpha-positive innate-type lymphocytes in the intestinal epithelium mediate mucosal immunity. Immunity 41, 451-464.

7. Wu, L., Parekh, V.V., Hsiao, J., Kitamura, D., and Van Kaer, L. (2014). Spleen supports a pool of innate-like B cells in white adipose tissue that protects against obesity-associated insulin resistance. Proc. Natl. Acad. Sci. USA 111, E4638-E4647.

8. Van Kaer, L., Wu, L., and Joyce, S. (2016). Feature Review: Mechanisms and consequences of antigen presentation by CD1. Trends Immunol. 37, 739-754.

9. Olivares-Villagomez, D., and Van Kaer, L. (2018). Review: Intestinal intraepithelial lymphocytes: sentinels of the mucosal barrier. Trends Immunol. 39, 264-275.

10. Wu, L., Dalal, R., Cao, C., Postoak, J.L., Yang, G., Zhang, Q., Wang, Z., Lal, H., and Van Kaer, L. (2019). IL-10-producing regulatory B cells are enriched in murine pericardial adipose tissues and ameliorate the outcome of acute myocardial infarction. Proc. Natl. Acad. Sci. USA 116, 21673-21684.

Autophagy in metabolic disease and immune cell function

1. Parekh, V.V., Wu, L., Boyd, K.L., Williams, J.A., Gaddy, J.A., Olivares-Villagómez, D., Cover, T.L., Zong, W.-X., Zhang, J., and Van Kaer, L. (2013). Impaired autophagy, defective T cell homeostasis and a wasting syndrome in mice with a T cell-specific deletion of Vps34. J. Immunol. 190, 5086-5101.

2. Parekh, V.V., Pabbisetty, S.K., Wu, L., Sebzda, E., Martinez, J., Zhang, J., and Van Kaer, L. (2017). Autophagy-related protein Vps34 controls the homeostasis and function of cross-presenting CD8a+ dendritic cells. Proc. Natl. Acad. Sci. USA Plus 114, E6371-E6380.

3. Yang, G., Song, W., Postoak, J.L., Chen, J., Martinez, J., Zhang, J., Wu, L., and Van Kaer, L. (2021). Brief Report:Autophagy-related protein PIK3C3/VPS34 controls T cell metabolism and function. Autophagy 17, 1193-1204.

4. Yang, G., Song, W., Xu, J., Postoak, J.L., Cheng, F., Martinez, J., Zhang, J., Wu, L., and Van Kaer, L. (2021). Pik3c3deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1b production. Cell. MolImmunol. 18, 2024-2039.

5. Yang, G., Postoak, J.L., Song, W., Martinez, J., Zhang, J., Wu, L., and Van Kaer, L. Brief Report: Dendritic cell PIK3C3/VPS34 controls the pathogenicity of CNS autoimmunity independently of LC3-associated phagocytosis. Autophagy, in press. doi: 10.1080/15548627.2021.1922051. Online ahead of print.

Other selected publications

1. Van Kaer, L., Ashton-Rickardt, P.G., Ploegh, H.L., and Tonegawa, S. (1992). TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell 71, 1205-1214.

2. Ashton-Rickardt, P.G., Van Kaer, L., Schumacher, T.N.M., Ploegh, H.L., and Tonegawa, S. (1993). Peptide contributes to the specificity of positive selection of CD8+ T cells in the thymus. Cell 73, 1041-1049.

3. Ashton-Rickardt, P.G., Bandeira, A., Delaney, J.R., Van Kaer, L., Pircher, H.-P., Zinkernagel, R.M., and Tonegawa, S. (1994). Evidence for a differential avidity model of T cell selection. Cell 76, 651-663.

4. Van Kaer, L., Ashton-Rickardt, P.G., Eichelberger, M., Gaczynska, M., Nagashima, K., Rock, K.L., Goldberg, A., Doherty, P., and Tonegawa, S. (1994). Altered peptidase and viral-specific T cell response in LMP2 mutant mice. Immunity 1, 533-541.

5. Martin, W.D., Hicks, G.G., Mendiratta, S.K., Leva, H.I., Ruley, H.E., and Van Kaer, L. (1996). H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Cell 84, 543-550.

6. Joyce, S., Negishi, I., Boesteanu, A., DeSilva, A.D., Sharma, P., Chorney, M.J., Loh, D.Y., and Van Kaer, L. (1996). Expansion of natural (NK1+) T cells that express ab T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice. J. Exp. Med. 184, 1579-1584.

7. Mendiratta, S.K., Martin, W.D., Hong, S., Boesteanu, A., Joyce, S., and Van Kaer, L. (1997). CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity 6, 469-477.

8. Sant’Angelo, D.B., Waterbury, P.G., Cohen, B.E., Martin, W.D., Van Kaer, L., Hayday, A.C., and Janeway, C.A., Jr. (1997). The imprint of intrathymic self-peptides on the mature T cell receptor repertoire. Immunity 7, 517-524.

9. Singh, N., Hong, S., Scherer, D.C., Serizawa, I., Burdin, N., Kronenberg, M., Koezuka, Y., and Van Kaer, L. (1999). Cutting Edge: Activation of NK T cells by CD1d and a-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. J. Immunol. 163, 2373-2377.

10. Singh, N., and Van Kaer, L. (1999). Unexpected reactivities of T cells selected by a single MHC-peptide ligand. J. Immunol. 163, 3583-3591.

11. Kovalik, J.-P., Singh, N., Mendiratta, S.K., Martin, W.D., Ignatowicz, L., and Van Kaer, L. (2000). The alloreactive and self-restricted CD4+ T cell response directed against a single MHC class II/peptide combination. J. Immunol. 165, 1285-1293.

12. Grandea, A.G. III, Golovina, T.N., Hamilton, S.E., Sriram, V., Spies, T., Brutkiewicz, R.R., Harty, J.H., Eisenlohr, L., and Van Kaer, L. (2000). Impaired assembly yet normal trafficking of MHC class I molecules in Tapasin mutant mice. Immunity 13, 213-222.

13. Shi, F.-D., Wang, H.-B., Li, H., Hong, S., Taniguchi, M., Link, H., Van Kaer, L., and Ljunggren, H.-G. (2000). Natural killer cells determine the outcome of B cell-mediated autoimmunity. Nature Immunol. 1, 245-251.

14. Hong, S., Wilson, M.T., Serizawa, I., Wu, L., Singh, N., Naidenko, O., Miura, T., Haba, T., Scherer, D.C., Wei, J., Kronenberg, M., Koezuka, Y., and Van Kaer, L. (2001). The natural killer T-cell ligand a-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nature Med. 7, 1052-1056.

15. Singh, A.K., Wilson, M.T., Hong, S., Olivares-Villagomez, D., Du, C., Stanic A.K., Koezuka, Y., Joyce, S., Sriram, S., and Van Kaer, L. (2001). Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J. Exp. Med. 194, 1801-1811.

16. Wilson, M.T., Johansson, C., Olivares-Villagomez, D., Singh, A.K., Stanic A.K., Wang, C.-R., Joyce, S., Wick, M.J., and Van Kaer, L. (2003). The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc. Natl. Acad. Sci. USA 100, 10913-10918.

17. Godfrey, D.I., MacDonald, H.R., Kronenberg, M., Smyth, M.J., and Van Kaer, L. (2004). Opinion: NKT cells: what’s in a name? Nature Rev. Immunol. 4, 231-237.

18. Van Kaer, L. (2004). Review: Natural killer T cells as targets for immunotherapy of autoimmune diseases. Immunol. Cell Biol. 82, 315-322.

19. Parekh, V.V., Singh, A.K., Wilson, M.T., Olivares-Villagomez, D., Bezbradica, J.S., Inazawa, H., Ehara, H., Sakai, T., Serizawa, I., Wu, L., Wang, C.-R., Joyce, S., and Van Kaer, L. (2004). Quantitative and qualitative differences in the in vivo response of NKT cells to distinct a- and b-anomeric glycolipids. J. Immunol. 173, 3693-3706.

20. Van Kaer, L. (2005). Review: a-Galactosylceramide therapy for autoimmune diseases: prospects and obstacles. Nature Rev. Immunol. 5, 31-42.

21. Singh, A.K., Yang, J.-Q., Parekh, V.V., Wei, J., Wang, C.-R., Joyce, S., Singh, R.R., and Van Kaer, L. (2005). The natural killer T cell ligand a-galactosylceramide prevents or promotes pristane-induced lupus in mice. Eur. J. Immunol. 35,1143-1154.

22. Bezbradica, J.S., Hill, T., Stanic, A.K., Van Kaer, L., and Joyce, S. (2005). Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc. Natl. Acad. Sci. USA 102, 5114-5119.

23. Parekh, V.V., Wilson, M.T., Olivares-Villagómez, D., Singh, A.K., Wu, L., Wang, C.-R., Joyce, S., and Van Kaer, L. (2005). Glycolipid antigen induces long-term natural killer T cell anergy in mice. J. Clin. Invest. 115, 2572-2583.

24. Beilke, J.N., Kuhl, N.R., Van Kaer, L., and Gill, R.G. (2005). NK cells promote islet allograft tolerance via a perforin-dependent mechanism. Nature Med. 11, 1059-1065.

25. Yan, J., Parekh, V.V., Mendez-Fernandez, Y., Olivares-Villagomez, D., Dragovic, S., Hill, T., Roopenian, D.C., Joyce, S., and Van Kaer, L. (2006). In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J. Exp. Med. 203, 647-659.

26. Major, A.S., Joyce, S., and Van Kaer, L. (2006). Review: Lipid metabolism, atherogenesis and CD1-restricted antigen presentation. Trends Mol. Med. 12, 270-278.

27. Bezbradica, J.S., Gordy, L.E., Stanic, A.K., Dragovic, S., Hill, T., Hawiger, J., Unutmaz, D., Van Kaer, L., and Joyce, S. (2006). Granulocyte-macrophage colony-stimulating factor regulates effector differentiation of invariant natural killer T cells during thymic ontogeny. Immunity 25, 487-497.

28. Shi, F.-D., and Van Kaer, L. (2006). Review: Reciprocal regulation between natural killer cells and autoreactive T cells. Nature Rev. Immunol. 6, 751-760.

29. Van Kaer, L. (2007). Review: NKT cells: T lymphocytes with innate effector functions. Curr. Opin. Immunol. 19, 354-364.

30. Adeeku, E., Gudapati, P., Mendez-Fernandez, Y., Van Kaer, L., and Boothby, M. (2008). Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors. Proc. Natl. Acad. Sci. USA 105, 9307-9312.

31. Parekh, V.V., Lalani, S., Kim, S., Halder, R., Azuma, M., Yagita, H., Kumar, V., Wu, L., and Van Kaer, L. (2009). PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J. Immunol. 182, 2816-2826.

32. Hoek, K.L., Gordy, L.E., Collins, P.L., Parekh, V.V., Aune, T.M., Joyce, S., Thomas, J.W., Van Kaer, L., and Sebzda, E. (2010). Follicular B cell trafficking within the spleen actively restricts humoral immune responses. Immunity 33, 254-265.

33. Goettel, J.A., Scott Algood, H.M., Olivares-Villagómez, D., Washington, M.K., Chaturvedi, R., Wilson, K.T., Van Kaer, L., and Polk, D.B. (2011). KSR1 protects from interleukin-10 deficiency-induced colitis in mice by suppressing T-lymphocyte interferon-g production. Gastroenterology 140, 265-274.

34. Shi, F.-D., Ljunggren, H.-G., La Cava, A., and Van Kaer, L. (2011). Review: Organ-specific features of natural killer cells. Nature Rev. Immunol. 11, 658-671.

35. Pabbisetty, S.K, Rabacal, W., Volanakis, E.J., Parekh, V.V., Olivares-Villagómez, D., Cedron, D., Boyd, K.L., Van Kaer, L., and Sebzda, E. (2016). Peripheral tolerance can be modified by altering KLF2-regulated Treg migration. Proc. Natl. Acad. Sci. USA 113, E4662-E4670.

36. Liu, Q., Sanai, N., Jin, W.-N., La Cava, A., Van Kaer, L., and Shi, F.-D. (2016). Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation. Nature Neurosci. 19, 243-252.

37. Celada, L.J., Kropski, J.A., Herazo-Mayo, J.D., Luo, W., Creecy, A., Abad, A.T., Chioma, O.S., Lee, G., Hassell, N.E., Shaginurova, G.I., Wang, Y., Johnson, J.E., Kerrigan, A., Mason, W.R., Baughman, R.P., Ayers, G.D., Bernard, G.R., Culver, D.A., Montgomery, C.G., Maher, T.M., Molyneaux, P.L., Noth, I., Mutsaers, S.E., Prele, C.M., Peebles, R.S., Newcomb, D.C., Kaminski, N., Blackwell, T.S., Van Kaer, L., and Drake, W.P. (2018). PD-1 upregulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-b1 production. Sci. Transl. Med. 10, Article eaar8356.

38. Kumar, A., Hill, T.M., Gordy, L.E., Suryadevara, N., Wu, L., Flyak, A.I., Bezbradica, J.S., Van Kaer, L., and Joyce, S. (2020). Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells. Proc. Natl. Acad. Sci. USA 117, 17156-17165.

39. Jin, W.-N., Shi, K., He, W., Sun, J.-H., Van Kaer, L., Shi, F.-D., and Liu, Q. (2021). Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition. Nature Neurosci. 24, 61-73.