Immune Dysfunctions

Overview

The SIgN Immune Dysfunctions program aims to characterize how immune homeostasis can be perturbed to result in immune dysregulation and disease manifestation, and how homeostasis can be recovered. Here, our researchers are investigating the basic principles underlying immune-cell ontogeny and differentiation, the environmental, genetic and aging-related factors that can trigger immune system dysregulation, and the identity of specific markers and signatures of dysregulation in order to develop new therapeutic interventions.

The program covers four main themes:

• Homeostasis: ontogeny, immune-regulation and inflammation

• Allergy: including airway, skin and drug-induced allergies

• Aging: involving immunosenescence and effects on metabolism and the microbiome

• Immunomonitoring: by deep immune-phenotyping, immunogenomics and studies of the immune-repertoire

Principal Investigators involved include:

Subhra BISWAS
Anna-Marie FAIRHURST
Katja FINK
Florent GINHOUX
Anis LARBI
Alessandra MORTELLARO
Evan NEWELL
Lai Guan NG
Norman PAVELKA
Michael POIDINGER
Ee Chee REN
Olaf ROTZSCHKE
Siew Cheng WONG

Click here to visit the Principal Investigators page. 

Research highlights

The data produced by researchers in this program is of high scientific excellence, as indicated by numerous successful publications in high impact journals including Immunity, Nature Immunology and the Journal of Experimental Medicine (see below). Furthermore, the studies conducted by our researchers have health, economic and industrial impact. Examples of the translational research conducted, and novel discoveries and innovative technologies contributed by the program include:

• immunoSCAPE, a multidimensional cell profiling (spin-off company)
• An advanced microscopy cluster for intravital organ imaging
• The dominance of a single allergen (dust mite) in tropical urban cities
• Identification of human dendritic cell precursors (patented)
• Development of a new platform for microbiome studies

Based on such developments, long-standing collaborative partnerships with a number of industry partners have been established, including Sanofi, Nestle, Servier, Merck, Galderma, L’Oreal, Danone, CIEA Japan, Becton Dickinson, Kyowa Hakko Kirin, Abbott and immunoSCAPE (local spin-off biotech).

Finally, the Immune Dysfunctions program has collaboratively established various cohorts for:

• Allergy — with the National University of Singapore
• Aging program & Sg90 cohort — with the Singapore Institute for Clinical Sciences and the National University of Singapore
• Skin program — with the Institute of Medical Biology, the Nanyang Technological University–Lee Kong Chian School of Medicine, and the Skin Research Institute of Singapore

The Immune Dysfunctions program has international collaborations with researchers including at: the Peter Doherty Institute, Australia; the University of Melbourne, Australia, the University of Sydney, Australia; the Shanghai Institute of Immunology, China.

Key Publications

•Evrard M et al. Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions. Immunity. 2018.
•McGovern N et al. Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2. Nature. 2017.
•See P et al. Mapping the human DC lineage through the integration of high-dimensional techniques. Science. 2017.
•Wong MT et al. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures. Immunity. 2016.
•Chong SZ et al. CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses. J Exp Med. 2016. 
•Simoni Y et al. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency. Immunity. 2016.
•Derny D et al. Complete human CD1a deficiency on Langerhans cells due to a rare point mutation in the coding sequence. J Allergy Clin Immunol. 2016. 
•Chen J et al. Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development. Nat Commun. 2016. 
•Andiappan AK et al. Functional variants of 17q12-21 are associated with allergic asthma but not allergic rhinitis. J Allergy Clin Immunol. 2016. 
•Schlitzer A et al. Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow. Nat Immunol. 2015. 
•Ginhoux F et al. New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat Immunol. 2015.
•Hoeffel G et al. C-myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity. 2015. 
•Andiappan AK at el. Genome-wide analysis of the genetic regulation of gene expression in human neutrophils. Nat Commun. 2015.
•Viganò E et al. Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes. Nat Commun. 2015.
•McGovern N et al. Human Dermal CD14+ Cells Are a Transient Population of Monocyte-Derived Macrophages. Immunity. 2014.

Click here to visit the full SIgN Publications page.