Immune Disease Institute

The Carroll lab is interested in understanding the role of the complement system in innate and acquired immunity and how it links the two systems via cell surface receptors. The lab’s research may lead to new therapies for lupus, reperfusion injury, and inflammatory and autoimmune conditions in general.

Innate immunity is the host’s first line of defense in recognition and response to any foreign invader, or non-self. While it is often referred to as a primitive immune system (relative to acquired immunity) it includes serum proteins (such as natural IgM) and receptors (such as Toll like receptors), which are highly specific for many pathogens (and certain self-antigens).

In acquired immunity, the complement system plays a critical role by marking antigen with a cleavage product of complement C3. Covalent attachment of this ligand to antigen is important for at least two reasons: (i) it enhances localization of antigen to the lymphoid compartment; (ii) it provides a ligand for B cell co-receptor which is essential for an effective B cell response.

The Carroll lab focuses on three main areas of basic research: (i) autoimmunity; (ii) inflammation; and (iii) host response to pathogens. Using genetic techniques, they develop novel strains of mice bearing altered innate or acquired immunity for study. Results from their studies of mouse models of systemic lupus erythematosus suggest that innate immunity is protective against autoimmune disease. The underlying mechanism, they believe, is due to a regulatory role of innate immunity (including complement) on tolerance of B lymphocytes.

In an animal model of inflammation, Carroll and colleagues have identified an essential role for natural IgM and complement in promoting an acute attack on self-tissues following periods of ischemia. They refer to this phenomena as "innate autoimmunity." These observations could explain a common mechanism for reperfusion injury-a life threatening disorder that follows myocardial infarction, stroke, general trauma, or surgery. Finally, the Carroll lab is exploring a murine model of influenza to identify the cellular and molecular basis for complement enhancement of acquired immunity to this highly infectious and lethal virus.

Michael Carroll received his Ph.D. in Immunology from the UT Southwestern Medical School (Dallas, TX) under the direction of Dr. J. Donald Capra in 1980; subsequently he trained with Dr. Rodney R. Porter in the Biochemistry Department, Oxford U (Oxford UK). In 1985, he was appointed an Assistant Professor in Pediatrics and the Department of Biological Chemistry at the Children’s Hospital/Harvard Medical School. He was promoted in 1998 to the rank of Professor of Pediatrics, Harvard Medical School and Senior Investigator, The Immune Disease Institute.