The research laboratory of the Department of Pulmonary Medicine focuses on fundamental, translational and clinical research concerning the pathology of various respiratory disorders. In this context, the research interests include the differentiation program of lymphoid cells in health and disease, using molecular approaches and animal models. The aims comprise the characterization of signal transduction pathways and lymphoid-specific transcription factors that implement cell fate decisions at specific checkpoints. One the one hand, there is a focus in the lab on the involvement of innate lymphoid cells and the T helper 2 subset in type II immunity, particularly in human allergic asthma and in mice. T cell subsets are also studied in a range of other respiratory disorders, including sarcoidosis and community-acquired pneumonia. On the other hand, there is a strong interest in B cell receptor signaling, particularly Bruton’s tyrosine kinase (BTK), both in B cell differentiation and in autoimmune inflammation in systemic autoimmunity and interstitial lung disease (ILD).
Education and career
Prof. dr. Rudi Hendriks studied Biology at the University of Utrecht, the Netherlands, and did his PhD studies on X chromosome inactivation patterns in human X-linked immunodeficiency diseases in the Department of Immunohaematology at the Leiden University Medical Center (Prof. J.J. van Rood; Dr. R.K.B. Schuurman) in 1991. After a post-doctoral training in the Genetics Laboratory of the University of Oxford, UK, where he studied genetic aspects of X chromosome inactivation, he started his own line of research within the lab of Prof. Frank Grosveld at the Department of Cell Biology and Genetics of the Erasmus MC Rotterdam, the Netherlands. In 1999 he moved his group to the Department of Immunology at the Erasmus MC, where he continued his research on the developmental program of lymphocytes in relation to immunodeficiency diseases and leukemia. Since Dr. Rudi W. Hendriks moved to the Department of Pulmonary Medicine in 2007, his research is focused on the role of B, T and innate lymphocytes in pulmonary immunity, in particular in allergic airway inflammation and autoimmune processes.
- KleinJan A, Tindemans I, Montgomery JE, Lukkes M, de Bruijn MJW, van Nimwegen M, Bergen I, Moellering RE, Hoogsteden HC, Boon L, Amsen D, Hendriks RW (2018). The Notch pathway inhibitor stapled α-helical peptide derived from mastermind-like 1 (SAHM1) abrogates the hallmarks of allergic asthma.
J Allergy Clin Immunol. 142:76-85.
- Tindemans I, Lukkes M, de Bruijn MJW, Li BWS, van Nimwegen M, Amsen D, KleinJan A, Hendriks RW (2017). Notch signaling in T cells is essential for allergic airway inflammation, but expression of the Notch ligands Jagged 1 and Jagged 2 on dendritic cells is dispensable.
J Allergy Clin Immunol. 140(4):1079-1089.
- Lim AI, Li Y, Lopez-Lastra S, Stadhouders R, Paul F, Casrouge A, Serafini N, Puel A, Bustamante J, Surace L, Masse-Ranson G, David E, Strick-Marchand H, Le Bourhis L, Cocchi R, Topazio D, Graziano P, Muscarella LA, Rogge L, Norel X, Sallenave JM, Allez M, Graf T, Hendriks RW, Casanova JL, Amit I, Yssel H, Di Santo JP (2017). Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation.
- Hendriks RW, Yuvaraj S and Kil L (2014). Targeting Bruton’s tyrosine kinase signaling in B cell malignancies.
Nature Rev. Cancer 14:219-232.
- Tindemans I, Serafini N, Di Santo JP and Hendriks RW (2014). GATA-3 function in innate and adaptive immunity.
In house-dust-mite-induced allergic airway inflammation, we found that ILC2 activation required T cells. Thus, in HDM-mediated airway inflammation in mice ILC2s do not provide an early innate source of IL-5/IL-13. Furthermore, the activation status of ILC2s was increased following influenza virus infection in mice, thereby likely contributing to inflammation-induced asthma exacerbation. Epigenetic analyses indicated that in circulating ILC2s ~80% of asthma-associated genes from GWAS were active, supporting a role for ILC2 in human asthma. In acute and chronic mouse models of HDM-mediated allergic asthma, we found that expression of Notch and its nuclear effector RBPJκ in T cells is essential for disease development. Mice lacking Jagged1/2 on DCs, T cells or lymph node stromal cells still developed HDM-driven airway inflammation. Importantly, hallmarks of asthma could be suppressed by the Notch inhibitory peptide SAHM1, which interferes with RBPJκ function. We also observed an increase in surface Notch1 and Notch2 positive TH2 cells in peripheral blood of asthma patients. Concerning our B cell work, we recently found that BTK protein levels and phosphorylation were increased in B cells from anti-citrullinated protein antibody (ACPA)-positive patients with rheumatoid arthritis, in Sjögren’s syndrome and in idiopathic pulmonary arterial hypertension.