Nicholas Arpaia, Ph.D.
Assistant Professor of Microbiology & Immunology
Ph.D., University of California, Berkeley
Mucosal immunity, tissue repair, immunometabolism, host-microbe interactions
Mounting an immune response is an energetically costly endeavor, with the potential to greatly impact host fitness. A cost-benefit relationship — between the collateral damage associated with an inflammatory response and the benefit of inflammation in protecting the host from infection — imparts a selective pressure that ensures the magnitude of a response is proportional to the potential threat encountered. To achieve homeostasis, the immune system must balance pro- and anti-inflammatory responses to neutralize invading pathogens while limiting or preventing damage to surrounding tissue. At mucosal barriers — which are colonized by diverse communities of commensal microbes and serve to interface the internal physiology of an organism with the ever-changing external environment — fine-tuning opposing immune responses is of even greater relevance. Constant exposure to novel environmental antigens and high concentrations of microbial ligands that can activate innate immune receptors increase the risk for persistent inflammatory activation. As a result, complex immune networks operate to contextualize diverse microbial and environmental stimuli. These inputs subsequently shape mucosal immune responses and synergize to preserve mucosal barrier integrity and function. Consequently, aberrant immune responses, due to a breakdown in tolerance or defects in barrier maintenance, largely underlie the etiology of chronic mucosal inflammatory disorders, including Crohn's disease and ulcerative colitis.
Our laboratory is interested in understanding how mucosal immune responses are coordinated to maintain homeostasis and respond to microbial infection, barrier disruption, or alterations in commensal microbial diversity — with an emphasis on how these molecular decisions are balanced within the context of host fitness and organ physiology. Our studies are geared toward uncovering pathways with the potential for therapeutic manipulation, specifically focusing on the signals that drive pro- and anti-inflammatory immune responses within each setting. Deciphering the molecular inputs that drive these opposing fates, and the subsequent cellular and molecular signals that immune cells employ, has applications in the treatment of infectious disease, cancer and autoimmune disorders.
For more information, visit our lab website.
Chowdhury, S., Castro, S., Coker, C., Hinchliffe, T.E., Arpaia, N.* and Danino, T.* (2019) Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nature Medicine DOI: https://doi.org/10.1038/s41591-019-0498-z *Co-corresponding
Kaiser, K.A. and Arpaia, N. (2018) Glycans for good. Science Immunol. 3: eaav1041.
Rankin, L.C. and Arpaia, N. (2018) Treg cells: A LAGging hand holds the double-edged sword of the IL-23 axis. Immunity 49: 201-203.
Yen, B., Fortson, K.T., Rothman, N.J., Arpaia, N.* and Reiner, S.L.* (2018) Clonal bifurcation of Foxp3 expression visualized in thymocytes and T cells. Immunohorizons 2: 119-128. *Co-corresponding
Green, J.A.*, Arpaia, N.*, Schizas, M., Dobrin, A. and Rudensky, A.Y. (2017) A nonimmune function of T cells in promoting lung tumor progression. J. Exp. Med. 214: 3565. *Co-equal
Arpaia, N., Green, J.A., Moltedo, B., Arvey, A., Hemmers, S., Yuan, S., Treuting, P.M. and Rudensky, A.Y. (2015) A distinct function of regulatory T cells in tissue protection. Cell 162: 1078-1089.
Jenq, R.R., Taur, Y., Devlin, S.M., Ponce, D.M., Goldberg, J.D., Ahr, K.F., Littmann, E.R., Ling, L., Gobourne, A.C., Miller, L.C., Docampo, M.D., Peled, J.U., Arpaia, N., Cross, J.R., Peets, T.K., Lumish, M.A., Shono, Y., Dudakov, J.A., Poeck, H., Hanash, A.M., Barker, J.N., Perales, M.A., Giralt, S.A., Pamer, E.G. and van den Brink M.R. (2015) Intestinal Blautia is associated with reduced death from graft-versus-host disease. Biol. Blood Marrow Transplant. 21: 1373-1383.
Arpaia, N. (2014) Keeping peace with the microbiome: acetate dampens inflammatory cytokine production in intestinal epithelial cells. Immunol. Cell Biol. 92: 561-562.
Sivick, K.E., Arpaia, N., Shu, J. and Barton, G.M. (2014) Toll-like receptor deficient mice reveal how innate immune signaling influences Salmonella virulence strategies. Cell Host and Microbe 15: 203-213.
Arpaia, N. and Rudensky, A.Y. (2014) Microbial metabolites control gut inflammatory responses. Proc. Natl. Acad. Sci. U.S.A. 111: 2058-2059.
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J.R., Pfeffer, K., Coffer, P.J. and Rudensky, A.Y. (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504: 451-455.
Arpaia, N. and Barton, G.M. (2013) The impact of Toll-like receptors on bacterial virulence strategies. Curr. Opin. Microbiol. 16: 17-22.
Mouchess, M.L., Arpaia, N., Souza, G., Barbalat, R., Ewald, S.E., Lau, L. and Barton, G.M. (2011) Transmembrane mutations in toll-like receptor 9 bypass the requirement for ectodomain proteolysis and induce fatal inflammation. Immunity 35: 1-12.
Arpaia, N. and Barton, G.M. (2011) Toll-like receptors: key players in antiviral immunity. Curr. Opin. Virol. 1: 1-8.
Arpaia, N., Godec, J., Lau, L., Sivick, K.E., McLaughlin, L.M., Jones, M.B., Dracheva, T., Peterson, S.N., Monack, D.M. and Barton, G.M. (2011) TLR signaling is required for Salmonella typhimurium virulence. Cell 144: 675-688.