Life science
Infectious diseases, Sepsis

Discovery of fibroblastic reticular cells that regulate body
cavity-associated lymphoid tissues
Immunology Frontier Research Center
Specially Appointed Associate Professor Yasutaka Okabe
https://researchmap.jp/7000018117?lang=en

Life science

Abstract
While abdominal cavity, which accomodates internal organs
such as the stomach, intestines, and pancreas, is normally sterile,infection can occur due to perforated appendicitis, liver cirrhosis,
pancreatitis, abdominal surgery, or peritoneal dialysis. The peritoneal infection can develop life-threatening sepsis which is characterized by bacteria and toxins spreading throughout the body andit causes multi-organ failure.
Visceral adipose tissue, omentum, is important organ for the protection from the peritoneal infection. Omentum harbors unique lymphoid structures called “milky spots” which plays a central role in
the peritoneal immune responses, whereas the mechanisms underlying the formation of these milky spots remain poorly understood.
In this study, we identified novel stromal cells that are responsible
for the formation of the milky spots.

▍ Background & Results
In this study, we conducted an analysis of stromal cells within theomental milky spots and identified novel fibroblastic reticular cells(FRCs) characterized by the production of retinoic acid. We termed
these cells as Aldh1a2+ FRCs. FRCs are special stromal cells thatform functionally compartmentalized structures in lymphoid tissues,

providing the “environment” for immune cell differentiation, activation, and maturation. Interestingly, Aldh1a2+ FRCs are specificallyfound in the omentum milky spots, whereas they were absent inother lymphoid tissues.
Furthermore, we revealed that Aldh1a2-positive FRCs induce theexpression of the chemokine CXCL12 in a specialized blood vessel
called a high endothelial venule (HEV) through the production ofretinoic acid. This discovery suggests that Aldh1a2-positive FRCs
play a role in controlling the recruitment of lymphocytes to thegreater omentum milky spots.

▍ Significance of the research and Future perspective
Sepsis is a life-threatening disease caused by infection and over
11 million deaths each year is estimated worldwide. Abdominal infections are reported as the second most common source of infection leading to sepsis, since bacteria and toxins in the peritoneal
cavity can easily spread throughout the body.
The omentum plays a crucial role in preventing the spread of
peritoneal infection, while its mechanism has not been fully understood. In this study, stromal cells essential for the formationof lymphoid tissues in the omentum have been identified. Further
development of the research may lead to a better understanding of
the mechanisms that prevent the spread of abdominal infections.

Aldh1a2+ FRC

Retinoic acidCXCL12
induction

Endothelial cellHEVCXCL12

Lymphocyte

Blood vessel

ALDH1A2+ FRCs regulate lymphocyte recruitment to the milky spot parenchyma via high endothelial venules (HEVs)

P a t e n t
Yoshihara, Tomomi; Okabe, Yasutaka. Aldh1a2+ fibroblastic reticular cells regulate lymphocyte recruitment in omental milky spots. The Journal ofExperimental Medicine. 2023, 220;e20221813. doi: 10.1084/jem.20221813
UR
L https://www.ifrec.osaka-u.ac.jp/en/laboratory/yasutaka_okabe/index.htm
K e y w o r d lymphoid organ, retinoic acid, stroma
Tr e a t i s e