REVIEW


Immune Physiology in Tissue Regeneration and Aging, Tumor Growth, and Regenerative Medicine

Antonin Bukovsky1, Michael R. Caudle1, Ray J. Carson2, Francisco Gaytán3, Mahmoud Huleihel4, Andrea Kruse5, Heide Schatten6, and Carlos M. Telleria7
1 Laboratory of Development, Differentiation and Cancer, Department of Obstetrics and Gynecology, The University of Tennessee College of Medicine and Graduate School of Medicine, Knoxville, TN 37920, USA
2 Department of Medical & Social Care Education, Leicester Medical School, University of Leicester, Leicester, LE1 9HN, UK
3 University of Cordoba, Department of Cell Biology, Physiology and Immunology, Cordoba, 14004, Spain
4 The Shraga Segal Department of Microbiology and Immunology, Beer-Sheva, 84105, Israel
5 Institute of Systemic Inflammation Research, University of Luebeck, Luebeck, 23538, Germany
6 University of Missouri; Columbia, MO 65211, USA
7 Division of Basic Biomedical Sciences, Sanford School of Medicine of The University of South Dakota, Vermillion, SD 57069, USA
Running title:
Immune Physiology in Mammals
Key words:
Immune physiology, tissue homeostasis, mesenchymal-epithelial interactions, proliferation, regeneration, aging, follicular renewal, animal models, tumor growth, regenerative medicine
Abbreviations:
CL, corpus luteum; CNS, central nervous system; DAZL, deleted azoospermia like; DC, dendritic cells; E2, estradiol; EICs, epithelial inclusion cysts; ESC, embryonic stem cells; MDC, monocyte-derived cells; MHC, major histocompatibility complex; NCAM, neural cell adhesion molecule; NSC, neural stem cells; OSC, ovarian stem cels; OSE, ovarian surface epithelium PG, progesterone; POF, premature ovarian failure; PRP, prime reproductive period; SCP3, meiotic entry synaptonemal complex protein-3; SSEA, stage-specific embryonic antigen; TCS, tissue control system; TCU, tissue control unit; TS, testosterone; ZP, zona pellucida
Received:
01/08/09; accepted: 02/10/09; published on line: 02/13/09
Correspondence:
E-mail:

Abstract

The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.