The overall focus in my laboratory is on the cellular and molecular mechanisms by which the nervous system influences immune and inflammatory functions. Specifically, we are interested in the role played by the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). CGRP and SP are found primarily in nerve endings of nociceptive (pain) fibers. CGRP and SP containing nerve endings are found around all blood vessels, in all internal and external surfaces (skin, muscal membranes, gastro-intestinal lining, etc.), in lymphoid organs and in bone marrow. They are released from these nerve endings in response to noxious stimuli (trauma, infection, etc.). Their release can also be induced by pro-inflammatory cytokines that are produced by inflammatory cells at local sites. Their overall function seems to be that they play an 'integrating role' in fine tuning vascular and cellular functions in local microenvironments.
Over the last decade our work has focused on CGRP. We first demonstrated that mature T and B lymphocytes have specific high affinity cell membrane receptors for CGRP. Work in our laboratory and several others has shown that CGRP has several effects on lymphocytes and macrophages, including inhibition of T cell proliferation and Ag presentation and both stimulatory and inhibitory effects on cytokine production. In the last couple of years we have focused on the role of CGRP in early B cell differentiation. We have recently completed a series of studies mapping CGRP receptor expression in developing B cells, and have shown that functional CGRP receptors are expressed at the earliest stages of B cell development. We have also shown that CGRP can inhibit multiple steps in early B cell differentiation by acting directly on developing B cells, and indirectly by stimulating production of inhibitory cytokines by stromal cells in the bone marrow. Current studies are addressing additional issues in terms of CGRP role in B cell development and function and its implications for health and disease.
McGillis, J.P, Fernandez, S., and Knopf, M.A. (2000) Regulation of immune and inflammatory reactions in local microenvironments by sensory neuropeptides. In: Psychoneuroimmunology, 3rd Ed. (Ader, B., Cohen, C., and Felten, D., eds.) Academic Press, NY, 217-229.
Fernandez, S. Knopf, M.A., and McGillis, J.P., (2000) Calcitonin gene-related peptide (CGRP) inhibits interleukin-7 induced proliferation of murine B cell precursors. Journal of Leukocyte Biology 67:669-676.
McGillis, J.P. and Fernandez, S.F. (1999) Neuropeptides, neurogenic inflammation and inflammatory cells. In: Progress in Inflammation Research. (S.D. Brain and P.K. Moore, eds.) Birkhauser Verlag, Basel, Switzerland, 115-135.
Mullins, M.W., Ciallella, J., Rangnekar, J., and McGillis, J.P. (1993) Characterization of a calcitonin gene related peptide receptor in mouse bone marrow. Regulatory Peptides, 49:65-72.
McGillis, J.P., Humphreys, S., Rangnekar, V., and Ciallella, J. (1993) Modulation of B lymphocyte differentiation by calcitonin gene related peptide (CGRP) II: Inhibition of ? light chain expression by CGRP. Cellular Immunology, 150:405-416.