Summary of Research
In 2009 Dr El Shikh discovered the ability of immune-complex-loaded follicular dendritic cells (FDCs) to induce T cell-independent immunity to T cell-dependent antigens in responses co-stimulated with FDC-derived BAFF and C4bBP. He has recently described a novel pathway of antigen processing and presentation by FDCs to B cells in germinal centres that is potentially involved in autoreactive B cell activation, breach of B cell tolerance, and perpetuation of autoimmunity. His recent findings that B cell tolerance to self-TNF-alpha, -IgE, -ECDII, and -HEL can be broken in well verified models of tolerance by self-antigen presentation by FDCs support the hypothesis that presentation of self/neo-antigens to B cells by activated FDCs induces autoreactive GC formation, auto-Ab secretion, and perpetuation of B cell autoimmunity. He is currently dissecting the molecular mechanisms underpinning this hypothesis which will not only advance our understanding of the mechanisms involved in autoreactive B cell activation and breakage of tolerance but also potentially open up a novel therapeutic avenue by inducing high affinity self-regulated auto-Abs to target endogenous mediators of chronic autoimmune and hypersensitivity diseases like TNF-alpha IgE, and ECDII.
Murine FDCs in LN GCs: (A) Activated GC B cells labeled with the mAb GL7 (green) are surrounded by a mantle of CD45Rhi (magenta) resting B cells in two adjacent secondary B cell follicles in the draining LNs of an immunised mouse. (B) These GC B cells downregulate CD45R expression upon activation. (C and D) The activated GC B cells are intimately associated with FDC Ag retaining reticulum (blue). (E) High magnification of the FDC reticulum retaining AMCA-conjugated ovalbumin (blue).
For a full list of publist publications click here
Follicular dendritic cells in health and disease. Frontiers in Immunology 3:292. El Shikh M., Pitzalis C. 2012. Follicular dendritic cells in health and disease. Frontiers in Immunology 3:292.
Tew, J. G., M. E. El Shikh, R. M. El Sayed, and H. A. Schenkein. 2012. Dendritic Cells, Antibodies Reactive with oxLDL, and Inflammation. J Dent.Res. 91:8-16.
El Shikh, M. E., R. El Sayed, M. Kmieciak, M. Manjili, A. Szakal, C. Pitzalis, and J. Tew. 2011. Breakage of B Cell Tolerance by Antigens on Follicular Dendritic Cells. Rheumatology 50:51.
Kikuchi, T., M. M. El Shikh, R. M. El Sayed, D. B. Purkall, M. M. Elaasser, A. Sarraf, S. E. Barbour, H. A. Schenkein, and J. G. Tew. 2010. Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells. J Periodontal Res. 45:720-730.
Ahmed, H. Y., H. H. El-Shiekh, E. A. Ghoneimy, A. M. Ragab, A. A. Saad, A. M. Hashem, R. M. El Sayed, and M. E. El Shikh. 2010. Fungal Secondary Metabolites: A Promising Source of Antineoplastic Drugs. Current Cancer Therapy Reviews 6:222-228.
El Shikh, M. E., R. M. El Sayed, S. Sukumar, A. K. Szakal, and J. G. Tew. 2010. Activation of B cells by antigens on follicular dendritic cells. Trends Immunol 31:205-211.
Gibb, D. R., M. El Shikh, D. J. Kang, W. J. Rowe, R. El Sayed, J. Cichy, H. Yagita, J. G. Tew, P. J. Dempsey, H. C. Crawford, and D. H. Conrad. 2010. ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo. J Exp.Med. 207:623-635.
El Shikh, M. E., R. M. El Sayed, A. K. Szakal, and J. G. Tew. 2009. T-independent antibody responses to T-dependent antigens: a novel follicular dendritic cell-dependent activity. J.Immunol. 182:3482-3491.
El Shikh, M. E., R. M. El Sayed, J. G. Tew, and G. F. Burton. 2009. Follicular Dendritic Cells (B Lymphocyte Stimulating). Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester.
Wu, Y., M. E. El Shikh, R. M. El Sayed, A. M. Best, A. K. Szakal, and J. G. Tew. 2009. IL-6 produced by immune complex-activated follicular dendritic cells promotes germinal center reactions, IgG responses and somatic hypermutation. Int.Immunol. 21:745-756.
Sukumar, S., M. E. El Shikh, J. G. Tew, and A. K. Szakal. 2008. Ultrastructural study of highly enriched follicular dendritic cells reveals their morphology and the periodicity of immune complex binding. Cell Tissue Res. 332:89-99.
Wu, Y., S. Sukumar, M. E. El Shikh, A. M. Best, A. K. Szakal, and J. G. Tew. 2008. Immune complex-bearing follicular dendritic cells deliver a late antigenic signal that promotes somatic hypermutation. J.Immunol. 180:281-290.
Abu Seadah, A. A. and M. E. El Shikh. 2008. RAPD typing of Aspergillus chevalieri, Aspergillus nidulans, Aspergillus tetrazonus (quadrilineatus) and their teleomorphs using 5'-d[AACGCGCAAC]-3' and 5'-d[CCCGTCAGCA]-3' primers. Mol.Biol.Rep. 35:89-95.
Daisy Vanitha John, Laura Crisa, Gabrielle Cauvi, M. E. El Shikh, J. G. Tew, and Bruce E Torbett. 2008. Primary human immune response to dendritic cell inoculation in humanized mice. FASEB J. 22:lb422.
El Shikh, M. E., R. M. El Sayed, J. G. Tew, and A. K. Szakal. 2007. Follicular dendritic cells stimulated by collagen type I develop dendrites and networks in vitro. Cell Tissue Res. 329:81-89.
El Shikh, M. E., R. M. El Sayed, Y. Wu, A. K. Szakal, and J. G. Tew. 2007. TLR4 on follicular dendritic cells: an activation pathway that promotes accessory activity. J.Immunol. 179:4444-4450.
El Shikh, M. E., R. El Sayed, A. K. Szakal, and J. G. Tew. 2006. Follicular dendritic cell (FDC)-FcgammaRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development. Eur.J.Immunol. 36:2715-2724.