CCR7 intimately links peripheral lymphocyte recirculation and mucosal tissue integrity
Continuous lymphocyte circulation from the blood into non-lymphoid tissues and from there back to local lymphoid organs via afferent lymphatics maintains immune surveillance under homeostatic as well as inflammatory conditions. We have recently shown that CCR7 controls not only trafficking to and within secondary lymphoid organs, but also homeostatic recirculation of lymphocytes through body cavities and non-lymphoid tissues. Lack of CCR7 resulted in a massive accumulation of B and T lymphocytes in body cavities and non-lymphoid epithelial tissues of CCR7-deficient mice. In the gastrointestinal tract, accumulated lymphocytes developed into functional ectopic lymphoid follicles. Flow cytometry analysis of CD4+ T cells derived from ectopic follicles revealed that CD44hiCD62Lloeffector memory T cells predominate in the gastric lymphoid aggregates. Moreover, lack of CCR7 induces age-dependent histomorphological changes in the stomach resulting in a severe hypertrophic gastropathy resembling Menetriers disease. Mechanistically, we have been able to demonstrate that adoptively transferred T and B lymphocytes require CCR7 expression to exit from peripheral sites via the afferent lymphatics into the draining lymph nodes. Thus, ectopic accumulation of lymphocytes is most likely caused by impaired egress of CCR7 deficient lymphocytes from non-lymphoid sites. We propose that CCR7 is ultimately required for the maintenance of homeostatic lymphocyte recirculation and mucosal tissue integrity.