Background/Purpose:

Tertiary lymphoid organs (TLOs) represent the histological hallmark of many immune-mediated inflammatory diseases. TLOs are characterized by a functional leukocyte aggregation and network of lymphoid-like stromal cells (LLSc). LLSc express lymphoid chemokines (CXCL13, CCL19, and CCL21), survival factors (BAFF and IL-7), lymphoid markers and adhesion molecules (gp38, RANKL, ICAM-1 and VCAM-1) that locally support lymphocytes survival and organization in ectopic sites areas. 

Methods:

We have used a combination of in vitro and in vivo approaches in two models of TLO formation to address the dynamic of stromal cell activation within TLOs.

Results and Conclusion:

We demonstrated that the acquisition of this lymphoid phenotype by the non-activated resident stroma requires a multistep process, fundamentally different from that responsible of secondary lymphoid organ formation. We showed that early, during TLO formation, IL-4Rα engagement via IL-13 on quiescent tissue-resident fibroblasts induces LLSc priming and mediates the up-regulation of gp38 and lymphoid-associated adhesion molecules. Expansion of this activated lymphoid stroma requires IL-22/IL-22R mediated signaling. Lack of IL-22 or its receptor induces defective LLS proliferation, abrogation of CXCL13 expression and TLO involution. Finally we demonstrated that, similarly to secondary lymphoid organ, stabilization of the stroma to a functional lymphoid phenotype requires lymphocyte infiltration and lymphotoxin beta expression. This work highlights critical differences between the embryonic program responsible for SLO formation and the inflammatory development of TLOs and unveils novel potential targets for TLO targeting.

---

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/tertiary-lymphoid-organ-developmental-program-diversgent-paradigm-of-lymphoid-organogenesis/