Selected Research and Reviews

Transcriptional control of central T cell tolerance by NR4A family nuclear receptors

Hailyn V. Nielsen, James L. Mueller, Ryosuke Hiwa, Letitia Yang, Irina Proekt, Elze Rackaityte, Dominik Aylard, Christopher D. Scharer, Mark Anderson, Byron Au-Yeung, Julie Zikherman. Biorxiv preprint. doi: https://doi.org/10.1101/2024.05.19.594881

summary: We show that the nuclear receptors Nr4a1 and Nr4a3 are essential to upregulate BIM and for thymic negative selection by tissue-restricted model self-antigen (TRA). Moreover, we reveal that the Nr4a family is absolutely required for full induction of a broad transcriptional program triggered in self-reactive thymocytes by TRA recognition, and conserved across model systems and the natural repertoire.

Molecular basis for potent B cell responses to antigen displayed on particles of viral size

Jeremy F. Brooks, Julianne Riggs, James L. Mueller, Raisa Mathenge, Wei-Yun Wholey, Sekou-Tidiane Yoda, Vivasvan Vykunta, Wei Cheng, Julie Zikherman. Nature Immunology. 2023 Oct;24(10):1762-1777. PMID: 37653247

summary: We show that multivalent epitope display on the surface of viral-sized particles functions as a ‘stand-alone’ danger signal by evading inhibitory pathways to trigger a unique mode of B cell receptor signaling. The activation, survival and proliferation of B cells stimulated with particulate antigen is highly enhanced compared with those stimulated with soluble antigen, and does not require co-stimulation from T cells.

NR4A nuclear receptors in T and B lymphocytes: Gatekeepers of immune tolerance.

Hiwa R, Brooks JF, Mueller JL, Nielsen HV, Zikherman J.

Immunological Reviews. 2022 Feb 17. PMID: 35174510

 

NR4A family members regulate T cell tolerance to preserve immune homeostasis and suppress autoimmunity

Ryosuke Hiwa, Hailyn V. Nielsen, James L. Mueller, Ravi Mandla, and Julie Zikherman.

JCI Insight 2021 Sep 8;6(17):151005. PMID: 34343134

 

Negative feedback by NUR77/Nr4a1 restrains B cell clonal dominance during early T-dependent immune responses

Jeremy F Brooks, Corey Tan, James L. Mueller, Kenta Hibiya, Ryosuke Hiwa, Julie Zikherman.

Cell Reports 2021 Aug 31;36(9):109645. PMID: 34469720

 

ATP-competitive partial antagonists of IRE-1α’s RNase segregate outputs of the UPR

Hannah C. Feldman, Rajarshi Ghosh, Vincent C. Auyeung, James L. Mueller, Jae-Hong Kim, Zachary E. Potter, Venkata N. Vidadala, B. Gayani K. Perera,

Alina Olivier, Bradley J. Backes, Julie Zikherman, Feroz R. Papa, Dustin J. Maly

Nature Chemical Biology 2021 Sep 23. PMID: 34556859

 

NR4A nuclear receptors restrain B cell responses to antigen when second signals are absent or limiting
Tan C, Hiwa R, Mueller JL, Vykunta V, Hibiya K, Noviski M, Huizar J, Brooks JF, Garcia J, Heyn C, Li Z, Marson A, Zikherman J.
Nature Immunology. 2020 Oct;21(10):1267-1279. PMID: 32868928

 

Optimal Development of Mature B Cells Requires Recognition of Endogenous Antigens

Mark Noviski, Corey Tan, John Huizar, Vivasvan Vykunta, James L. Mueller and Julie Zikherman. J Immunol. 2019 Jul 15;203(2):418-428. PMID: 31167773

Nur77 Links Chronic Antigen Stimulation to B Cell Tolerance by Restricting the Survival of Self-Reactive B Cells in the Periphery.
Tan C, Mueller JL, Noviski M, Huizar J, Lau D, Dubinin A, Molofsky A, Wilson PC, Zikherman J.
J Immunol. 2019 May 15;202(10):2907-2923. PMID: 30962292

 

IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate.
Noviski M, Mueller JL, Satterthwaite A, Garrett-Sinha LA, Brombacher F, Zikherman J.
Elife. 2018 Mar 9;7. pii: e35074. PMID: 29521626

 

Nur77 Is Upregulated in B-1a Cells by Chronic Self-Antigen Stimulation and Limits Generation of Natural IgM Plasma Cells
Huizar J, Tan C, Noviski M, Mueller JL, Zikherman J.
ImmunoHorizons. November 1, 2017, 1 (9) 188-197. PMID: 29152611

 

IL-2 Modulates the TCR Signaling Threshold for CD8 but Not CD4 T Cell Proliferation on a Single-Cell Level.
Au-Yeung BB, Smith GA, Mueller JL, Heyn CS, Jaszczak RG, Weiss A, Zikherman J.
J Immunol. 2017 Mar 15;198(6):2445-2456. PMID:28159902

 

An extracatalytic function of CD45 in B cells is mediated by CD22.
Coughlin S, Noviski M, Mueller JL, Chuwonpad A, Raschke WC, Weiss A, Zikherman J.
Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):E6515-24. PMID:26561584

 

Cutting edge: An in vivo reporter reveals active B cell receptor signaling in the germinal center.
Mueller J, Matloubian M, Zikherman J.
J Immunol. 2015 Apr 1;194(7):2993-7. PMID:25725108

 

A sharp T-cell antigen receptor signaling threshold for T-cell proliferation.
Au-Yeung BB, Zikherman J, Mueller JL, Ashouri JF, Matloubian M, Cheng DA, Chen Y, Shokat KM, Weiss A.
Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3679-88. 1413726111.

 

Endogenous antigen tunes the responsiveness of naive B cells but not T cells.
Zikherman J, Parameswaran R, Weiss A.
Nature. 2012 Sep 6;489(7414):160-4. PMID: 22902503

 

Complete List of Publications