Steven J. Van Dyken, Ph.D.

Assistant Professor
Pathology and Immunology

Immunology Program
Developmental, Regenerative and Stem Cell Biology Program
Molecular Microbiology and Microbial Pathogenesis Program

  • 314-273-2520

  • 314-273-2525

  • 314-747-0809

  • 8112 BJC Institute of Health

  • svandyken@wustl.edu

  • https://sites.wustl.edu/vandykenlab/

  • Cytokine-mediated tissue feedback loops that maintain homeostasis, and environmental factors that instigate inflammation and fibrosis.

Research Abstract:

Our research focuses on how immune cells integrate multiple signals to maintain homeostasis within their resident tissues. In many cases, this molecular dialogue is initiated by epithelial cells and innate lymphoid cells (ILCs), which produce hallmark cytokines that reflect subsequent adaptive immune responses mediated by T cells. We are interested in how ILC- and T cell-derived cytokines amplify normal tissue functions to maintain organ health. One such function is the degradation of chitin, a widespread polysaccharide and constituent of fungi, helminths and arthropods. Chitin activates a robust immune response that converges on tissue-resident lymphoid cells, particularly ILC2s, which communicate with epithelial cells via cytokines to boost production of chitinases, specialized chitin-degrading enzymes. These enzymes break down insoluble chitin, thereby relieving the immune stimulus and restoring normal tissue function. Indeed, in the absence of this feedback system, environmentally-derived chitin polymers accumulate abnormally in mammalian tissues, provoking chronic inflammation, fibrosis, and early mortality. Understanding tissue-restricted cytokine feedback loops may thus inform treatment strategies for chronic inflammatory diseases associated with ill-defined tissue remodeling and regenerative pathways. We employ cutting-edge in vivo and in vitro approaches to decode the specific signals that organize these loops in development, tissue injury, and infection to determine whether they can be manipulated to regulate barrier integrity and organ health.

Selected Publications:

Ricardo-Gonzales RR,* Van Dyken SJ,* Schneider C, Lee J, Nussbaum JC, Liang HE, Vaka D, Eckalbar WL, Molofsky AB, Erle DJ, Locksley RM. Tissue signals imprint ILC2 identity with anticipatory function. Nat. Immunol. (in press). *Equal contribution.

Van Dyken SJ, Locksley RM. Chitins and chitinase activity in airway diseases. J Allergy Clin Immunol. 2018 Aug;142(2):364-369. PubMed PMID: 29959948; NIHMSID: NIHMS980146; PubMed Central PMCID: PMC6078791.

Van Dyken SJ, Liang HE, Naikawadi RP, Woodruff PG, Wolters PJ, Erle DJ, Locksley RM. Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease. Cell. 2017 Apr 20;169(3):497-509.e13. PubMed PMID: 28431248; PubMed Central PMCID: PMC5444468.

Van Dyken SJ,* Nussbaum JC,* Lee J, Molofsky AB, Liang HE, Pollack JL, Gate RE, Haliburton GE, Ye CJ, Marson A, Erle DJ, Locksley RM. A tissue checkpoint regulates type 2 immunity. Nat Immunol. 2016 Dec;17(12):1381-1387. PubMed PMID: 27749840; PubMed Central PMCID: PMC5275767. *Equal contribution.

Van Dyken SJ, Mohapatra A, Nussbaum JC, Molofsky AB, Thornton EE, Ziegler SF, McKenzie AN, Krummel MF, Liang HE, Locksley RM. Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and γδ T cells. Immunity. 2014 Mar 20;40(3):414-24. PubMed PMID: 24631157; PubMed Central PMCID: PMC4019510.

Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013 31:317-43. PubMed PMID: 23298208; PubMed Central PMCID: PMC3606684.

Van Dyken SJ, Garcia D, Porter P, Huang X, Quinlan PJ, Blanc PD, Corry DB, Locksley RM. Fungal chitin from asthma-associated home environments induces eosinophilic lung infiltration. J Immunol. 2011 Sep 1;187(5):2261-7. PubMed PMID: 21824866; PubMed Central PMCID: PMC3159725.

Van Dyken SJ, Green RS, Marth JD. Structural and mechanistic features of protein O-glycosylation linked to CD8+ T-cell apoptosis. Mol Cell Biol. 2007 Feb;27(3):1096-111. PubMed PMID: 17101770; PubMed Central PMCID: PMC1800694.

Last Updated: 9/10/2018 9:28:27 AM

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