Abstract
The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs (SLO) occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional lymphoid tissue inducer (LTi) cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to SLO formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood. Recently, new findings revealed early phases of SLO development putting emphasis on mesenchymal and lymphoid tissue initiator cells. Herein we discuss the main tenets of enteric lymphoid organs genesis and focus in the most recent findings that open new perspectives to the understanding of the early phases of lymphoid morphogenesis.
Highlights
The lymphoid system possesses highly specialized peripheral organs formed at strategic anatomical sites that constitute threedimensional platforms ensuring efficient immune-surveillance, rapid immune responses and maintenance of protective immunity
While lymph nodes (LN) develop at strictly invariable locations along lymphatic vessels, Peyer’s patches (PP) develop in variable number and position in the anti-mesenteric side of the mid-intestine (5–12 in mice; Nishikawa et al, 2003)
Secondary lymphoid organs (SLO) development relies on an antigen-independent process where presumptive regions are colonized by lymphoid tissue inducer (LTi) cells that crosstalk with resident mesenchymal cells through lymphotoxin (LT) α1β2 and LTβ receptor (LTβR) interactions, creating a positive feed-back loop that culminates on the anlagen formation
Summary
Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal. Reviewed by: Mark Christopher Coles, University of York, UK Sanjiv A. The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs (SLO) occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is well established that the recruitment of fully functional lymphoid tissue inducer (LTi) cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to SLO formation. New findings revealed early phases of SLO development putting emphasis on mesenchymal and lymphoid tissue initiator cells. We discuss the main tenets of enteric lymphoid organs genesis and focus in the most recent findings that open new perspectives to the understanding of the early phases of lymphoid morphogenesis
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