TY - JOUR
T1 - Vagal innervation is required for the formation of tertiary lymphoid tissue in colitis
AU - Olivier, Brenda J.
AU - Cailotto, Cathy
AU - van der Vliet, Jan
AU - Knippenberg, Marlene
AU - Greuter, Mascha J.
AU - Hilbers, Francisca W.
AU - Konijn, Tanja
AU - te Velde, Anje A.
AU - Nolte, Martijn A.
AU - Boeckxstaens, Guy E.
AU - de Jonge, Wouter J.
AU - Mebius, Reina E.
PY - 2016/10
Y1 - 2016/10
N2 - Tertiary lymphoid tissue (TLT) is lymphoid tissue that forms in adult life as a result of chronic inflammation in a tissue or organ. TLT has been shown to form in a variety of chronic inflammatory diseases, though it is not clear if and how TLT develops in the inflamed colon during inflammatory bowel disease. Here, we show that TLT develops as newly formed lymphoid tissue in the colon following dextran sulphate sodium induced colitis in C57BL/6 mice, where it can be distinguished from the preexisting colonic patches and solitary intestinal lymphoid tissue. TLT in the inflamed colon develops following the expression of lymphoid tissue-inducing chemokines and adhesion molecules, such as CXCL13 and VCAM-1, respectively, which are produced by stromal organizer cells. Surprisingly, this process of TLT formation was independent of the lymphotoxin signaling pathway, but rather under neuronal control, as we demonstrate that selective surgical ablation of vagus nerve innervation inhibits CXCL13 expression and abrogates TLT formation without affecting colitis. Sympathetic neuron denervation does not affect TLT formation. Hence, we reveal that inflammation in the colon induces the formation of TLT, which is controlled by innervation through the vagus nerve
AB - Tertiary lymphoid tissue (TLT) is lymphoid tissue that forms in adult life as a result of chronic inflammation in a tissue or organ. TLT has been shown to form in a variety of chronic inflammatory diseases, though it is not clear if and how TLT develops in the inflamed colon during inflammatory bowel disease. Here, we show that TLT develops as newly formed lymphoid tissue in the colon following dextran sulphate sodium induced colitis in C57BL/6 mice, where it can be distinguished from the preexisting colonic patches and solitary intestinal lymphoid tissue. TLT in the inflamed colon develops following the expression of lymphoid tissue-inducing chemokines and adhesion molecules, such as CXCL13 and VCAM-1, respectively, which are produced by stromal organizer cells. Surprisingly, this process of TLT formation was independent of the lymphotoxin signaling pathway, but rather under neuronal control, as we demonstrate that selective surgical ablation of vagus nerve innervation inhibits CXCL13 expression and abrogates TLT formation without affecting colitis. Sympathetic neuron denervation does not affect TLT formation. Hence, we reveal that inflammation in the colon induces the formation of TLT, which is controlled by innervation through the vagus nerve
KW - Chemokines
KW - Dextran sodium sulphate colitis model
KW - Stromal cells
KW - Tertiary lymphoid tissue
KW - Vagus nerve
U2 - https://doi.org/10.1002/eji.201646370
DO - https://doi.org/10.1002/eji.201646370
M3 - Article
C2 - 27457277
SN - 0014-2980
VL - 46
SP - 2467
EP - 2480
JO - European journal of immunology
JF - European journal of immunology
IS - 10
ER -