Cellular and genetic factors involved in the difference between Brown Norway and Lewis rats to develop respectively type‐2 and type‐1 immune‐mediated diseases

Fournié, Gilbert J.; Cautain, Bastien; Xystrakis, Emmanuel; Damoiseaux, Jan; Mas, Magali; Lagrange, Dominique; Bernard, Isabelle; Subra, Jean‐François; Pelletier, Lucette; Druet, Philippe; Saoudi, Abdelhadi

doi:10.1034/j.1600-065x.2001.1840114.x

Cited by 76 publications

(80 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fact that DC subsets could influence Th1 or Th2 responses (5) makes the difference between the Lewis and BN strains especially relevant. Indeed, Lewis rats are known to be prone to several Th1-mediated autoimmune diseases while being resistant to those mediated by Th2, whereas BN rats behave oppositely (31). Moreover, we showed that CD4 ϩ DC were the only DC subset to promote IL-13-producing CD4 ϩ T cells (25) and that mature pDC drive Th1 differentiation (24).…”

Section: Discussionmentioning

confidence: 67%

Differential Pattern Recognition Receptor Expression but Stereotyped Responsiveness in Rat Spleen Dendritic Cell Subsets

Hubert

Voisine

Louvet

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Dendritic cells (DC) are a heterogeneous population of APC endowed with specific functions. The nature of the DC subset involved in the course of an immune response to a specific pathogen might be important for inducing the appropriate effectors. In addition, each DC subset might also exhibit intrinsic functional plasticity. In the rat, spleen DC can be separated into three morphological and phenotypical distinct subsets, namely CD4+, CD4−, and plasmacytoid DC (pDC), whose frequencies are strain dependent. We correlated the expression of TLR and nucleotide-binding oligomerization domain 2 (NOD2) in these DC subsets to their in vitro responsiveness to specific ligands. CD4− DC expressed high levels of TLR1, 2, 3, and 10 mRNA, low TLR4, 5, 6, 7, and 9, and very low, if any, TLR8. pDC had a restricted repertoire characterized by high TLR7 and 9. CD4+ DC expressed all TLR and 10-fold higher levels of NOD2 mRNA than CD4− and pDC. Upon stimulation by TLR and NOD2 ligands, each DC subset responded in quite a stereotyped fashion. TLR2/6, 3, 4, 5, 9, and NOD2 triggering induced CD4− DC to mature and produce high IL-12p40, low IL-10, and TNF-α. TLR7/8 and 9 triggering induced pDC to mature and produce copious amounts of IL-6, IL-12p40, and TNF-α and low IFN-α. CD4+ DC were very poor producers of inflammatory cytokines. This study suggests that the nature of spleen DC responses to pathogens is dependent on subset specific-stimulation rather than intrinsic plasticity.

show abstract

Section: Discussionmentioning

confidence: 67%

Differential Pattern Recognition Receptor Expression but Stereotyped Responsiveness in Rat Spleen Dendritic Cell Subsets

Hubert

Voisine

Louvet

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Thus the Lewis mounts a Th1 response and is susceptible to EAE and autoimmune uveoretinitis, both Th1 mediated, while the BN is susceptible to mercuric chloride-induced glomerulopathy 35 and gold salts autoimmunity, 36 both Th2 responses. Cautain et al 25 suggested that the natural resistance of the BN to EAE is associated with a defect in the ability to mount a Th1 response.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Contributes to Resistance of the Brown Norway Rat to Experimental Autoimmune Encephalomyelitis

Staykova

Paridaen

Cowden

et al. 2005

The American Journal of Pathology

View full text Add to dashboard Cite

The Brown Norway (BN) rat is reported to be resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and a number of mechanisms have been suggested to explain this resistance. In work reported here we provide evidence that such resistance in the BN rat can be accounted for, at least in part, by their ability to produce higher levels of nitric oxide (NO) than susceptible strains of rats. Spleen cells from the BN rat make significantly more NO following in vitro stimulation than do cells from the Lewis or PVG rat and following in vivo immunization using complete Freund's adjuvant (CFA) the BN rat makes substantially more NO than either susceptible strain. If carbonyl iron is used as adjuvant in vivo there is no increase in NO levels in the BN rat and they are rendered highly susceptible to EAE. Immunizing with CFA simultaneously with neuroantigen and carbonyl iron drives up NO levels and the resistance is restored. EAE produced using carbonyl iron is characterized by extensive macrophage/microglia presence in the central nervous system lesions of the BN rat yet the cytokine profile in the lymph nodes does not differ from that in the EAE Lewis rats. Nitric oxide (NO) is a free radical produced from the oxidation of the terminal guanidino nitrogen of arginine; the reaction is catalyzed by an NADPH-dependent enzyme, nitric oxide synthase (NOS) of which three isoforms have been described.

show abstract

“…A number of unusual cellular immunological phenotypes have been reported, such as a high CD4:CD8 T cell ratio (34), skewed CD45RC expression (35), and low mitogen responsiveness (36,37). Although good progress is being made toward the genetic dissection of these phenotypes (38), this work is not complete and it will be interesting to determine whether the BN Gimap4 variant, as a T cell GTPase apparently susceptible to regulation through the TCR (14 -16), plays any part in them. To this end a BN congenic strain carrying the PVG (wild type) Gimap4 is under preparation.…”

Section: Discussionmentioning

confidence: 99%

A Natural Hypomorphic Variant of the Apoptosis Regulator Gimap4/IAN1

Carter

Dion

Schnell

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

The Gimap/IAN family of GTPases has been implicated in the regulation of cell survival, particularly in lymphomyeloid cells. Prosurvival and prodeath properties have been described for different family members. We generated novel serological reagents to study the expression in rats of the prodeath family member Gimap4 (IAN1), which is sharply up-regulated at or soon after the stage of T cell-positive selection in the thymus. During these investigations we were surprised to discover a severe deficiency of Gimap4 expression in the inbred Brown Norway (BN) rat. Genetic analysis linked this trait to the Gimap gene cluster on rat chromosome 4, the probable cause being an AT dinucleotide insertion in the BN Gimap4 allele (AT(+)). This allele encodes a truncated form of Gimap4 that is missing 21 carboxyl-terminal residues relative to wild type. The low protein expression associated with this allele appears to have a posttranscriptional cause, because mRNA expression was apparently normal. Spontaneous and induced apoptosis of BN and wild-type T cells was analyzed in vitro and compared with the recently described mouse Gimap4 knockout. This revealed a “delayed” apoptosis phenotype similar to but less marked than that of the knockout. The Gimap4 AT(+) allele found in BN was shown to be rare in inbred rat strains. Nevertheless, when wild rat DNA samples were studied the AT(+) allele was found at a high overall frequency (∼30%). This suggests an adaptive significance for this hypomorphic allele.

show abstract

Cellular and genetic factors involved in the difference between Brown Norway and Lewis rats to develop respectively type‐2 and type‐1 immune‐mediated diseases

Cited by 76 publications

References 2 publications

Differential Pattern Recognition Receptor Expression but Stereotyped Responsiveness in Rat Spleen Dendritic Cell Subsets

Differential Pattern Recognition Receptor Expression but Stereotyped Responsiveness in Rat Spleen Dendritic Cell Subsets

Nitric Oxide Contributes to Resistance of the Brown Norway Rat to Experimental Autoimmune Encephalomyelitis

A Natural Hypomorphic Variant of the Apoptosis Regulator Gimap4/IAN1

Contact Info

Product

Resources

About