Lochner, M. et al. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORgamma t and LTi cells. J. Exp. Med. 208, 125-134

Lymphoid Tissue Development Unit, Institut Pasteur, 75724 Paris, France.
Journal of Experimental Medicine (Impact Factor: 13.91). 01/2011; 208(1):125-134. DOI: 10.1084/jem.20100052
Source: PubMed

ABSTRACT The programmed development of lymph nodes and Peyer’s patches during ontogeny requires lymphoid tissue inducer (LTi) cells
that express the nuclear hormone receptor RORγt. After birth, LTi cells in the intestine cluster into cryptopatches, the precursors
of isolated lymphoid follicles (ILFs), which are induced to form by symbiotic bacteria and maintain intestinal homeostasis.
We show that in RORγt-deficient mice, which lack LTi cells, programmed lymphoid tissues, ILFs, and Th17 cells, bacterial containment
requires the generation of large numbers of tertiary lymphoid tissues (tLTs) through the activity of B cells. However, upon
epithelial damage, these mice develop severe intestinal inflammation characterized by extensive recruitment of neutrophils
and IgG+ B cells, high expression of activation-induced deaminase in tLTs, and wasting disease. The pathology was prevented by antibiotic
treatment or inhibition of lymphoid tissue formation and was significantly decreased by treatment with intravenous immunoglobulin
G (IVIG). Our data show that intestinal immunodeficiency, such as an absence in RORγt-mediated proinflammatory immunity, can
be compensated by increased lymphoid tissue genesis. However, this comes at a high cost for the host and can lead to a deregulated
B cell response and aggravated inflammatory pathology.

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Available from: Caspar Ohnmacht, Aug 23, 2015
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    • "Accordingly, the severity of disease was also reduced when wild-type cells including Th17 cells were transferred back into RORgt-deficient mice. The prime cause of the severe pathology induced in RORgt-deficient mice by DSS was penetration by the microbiota: development of disease was completely blocked by treatment with antibiotics (Lochner et al., 2011b). Thus, even though during steady state, these mice could compensate their loss of pro-inflammatory immunity through the production of IgG against symbionts , among several mechanisms probably, this strategy was fatal when bacterial penetration was augmented. "
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