Immunology Faculty Member - Michael Carroll, PhD

Michael Carroll, PhD

Co-Director, Master's program in Immunology

Boston Children's Hospital
200 Longwood Ave.
WAB, Room 251
Boston, MA 02115
Tel: 617-713-8700
Fax: 617-713-8702
Email: michael.carroll@childrens.harvard.edu
Visit my lab page here.



OVERVIEW
My lab’s research interests are focused in two broad areas, i.e. autoimmunity and neuro-immunology.

Autoimmunity
SLE is an incurable autoimmune disease characterized by anti-nuclear antibodies (ANA). One current view is that disease is initiated by a “rogue” B cell that escapes negative selection and secretes pathogenic antibody against nuclear antigen eventually leading to formation of germinal centers and expansion of autoimmunity to include antibodies to many tissue antigens such as skin and kidney. Disease is amplified by activation of the complement system and secretion of inflammatory cytokines. In order to understand how self-reactive B cells are regulated, we use murine models of autoimmunity and conditional reporter mice that bear deficiencies in genes involved in normal adaptive immunity.

Some important questions in the field are:
1. What initiates the escape of tolerance by a Rogue B cell?
2. How does the dysregulation of a Rogue B cell result in chronic autoimmunity?
3. What are the events that lead to spreading of the initial response to other tissue antigens?

Neuroimmunology
It is increasingly evident that the brain is not isolated from events in the peripheral immune system and that innate pathways important in host protection can become dysregulated leading to neuropsychiatric changes. For example, increased copy number of the human complement C4A gene is a major risk factor for Schizophrenia; while in the periphery, it is protective against systemic autoimmunity such as lupus. Elevation in peripheral levels of interferon alpha (IFN-
a) such as in viral infection, autoimmunity, interferonopathies or treatment with recombinant cytokine are strongly associated with psychiatric symptoms. We propose that blood-brain barrier entry of inflammatory cytokines such as IFN-a can activate multiple cell types in the brain triggering excess pruning of synapses altering neural circuits critical in executive function and cognitive memory.

Some important questions in the field are:
1. Does “too much” expression of C4A promote loss of synapses leading to schizophrenia?
2. What are the cell sources and regulation of the complement system in the brain?
3. Does entry of IFN-
a lead to targeting of specific neural circuits by activated microglia?



Last Update: 8/30/2019



Publications

Das A, Heesters BA, Bialas A, O'Flynn J, Rifkin IR, Ochando J, Mittereder N, Carlesso G, Herbst R, Carroll MC. Follicular dendritic cell activation by TLR ligands promotes autoreactive B cell responses. Immunity 2017, 46 (1); 106-119. PMID: 28099860.

Degn SE, Van der Poel C, Firl DJ, Ayoglu B, Al Qureshah FA, Bajic G, Mesin L, Reynaud CA, Weill J-C, Utz PJ, Victora GD and Carroll MC. Clonal Evolution of Autoreactive Germinal Centers. Cell 2017; 170 (5); 913-926; PMID:28841417.

Firl DJ, Degn SE, Padera, TP and Carroll MC. Capturing change in clonal composition
amongst single mouse germinal centers. eLife 2018;

Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V, Genovese G, Rose SA, Handsaker RE; Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly MJ, Carroll MC, Stevens B, McCarroll SA. Schizophrenia risk from complex variation of complement component 4. Nature 2016; 530 (7589); 177-83. PMCID 4752392.

Chatterjee P, Agyemang AF, Alimzhanov MB, Degn S, Tsiftsoglou SA, Alicot E, Jones SA, Ma M, Carroll MC. Complement C4 maintains peripheral B-cell tolerance in a myeloid cell-dependent manner. Eur J Immunol. 2013 Sep;43(9):2441-50.

Balthasar A. Heesters, Priyadarshini Chatterjee, Young-A. Kim, Santiago F. Gonzalez, Michael P. Kuligowski, Tomas Kirchhausen, Michael C. Carroll.
Endocytosis and Recycling of Immune Complexes by Follicular Dendritic Cells Enhances B Cell Antigen Binding and Activation. Immunity. 2013 June 27;38(6): 1164-75.

Woodruff MC, Herndon CN, Heesters BA, Carroll MC. Contextual analysis of immunological response through whole-organ fluorescent imaging. Lymphat Res Biol. 2013 Sep;11(3):121-7.



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of Harvard College