Journal article
Estrogen Receptor-1 (Esr1) and -2 (Esr2) Regulate the Severity of Clinical Experimental Allergic Encephalomyelitis in Male Mice
The American journal of pathology, v 164(6), pp 1915-1924
Jun 2004
PMID: 15161628
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Abstract
Estrogens and estrogen-receptor signaling function in establishing and regulating the female immune system and it is becoming increasingly evident that they may play a similar role in males. We report that B10.PL/SnJ male mice with a disrupted estrogen receptor-1 (α) gene (
Esr1
−/−
) develop less severe clinical experimental allergic encephalomyelitis (EAE) compared to either
Esr1
+/−
or wild-type (
Esr1
+/+
) controls when immunized with myelin basic protein peptide Ac1-11 (MBP
Ac1-11
). In contrast, the disease course in B10.PL/SnJ male mice with a disrupted estrogen receptor-2 (β) gene (
Esr2
−/−
) does not differ from that of wild-type (
Esr2
+/+
) mice. However,
Esr2
+/−
mice do develop more severe clinical disease with an earlier onset indicating that heterosis at
Esr2
plays a significant role in regulating EAE in males. No significant differences in central nervous system histopathology or MBP
Ac1-11
-specific T-cell responses as assessed by proliferation and interleukin-2 production were observed as a function of either
Esr1
or
Esr2
genotype. An analysis of cytokine/chemokine secretion by MBP
Ac1-11
-specific T cells revealed unique
Esr1
and
Esr2
genotype-dependent regulation. Interferon-γ secretion was found to be negatively regulated by
Esr1
whereas interleukin-6 and tumor necrosis factor-α secretion exhibited classical
Esr2
gene dose responses. Interestingly, MCP-1 displayed distinctively unique patterns of genotype-dependent regulation by
Esr1
and
Esr2
. The contribution of the hematopoietic and nonhematopoietic cellular compartments associated with the heterotic effect at
Esr2
in regulating the severity of clinical EAE was identified using reciprocal hematopoietic radiation bone marrow chimeras generated between male wild-type and
Esr2
+/−
mice. Wild-type →
Esr2
+/−
mice exhibited EAE equivalent in severity to that seen in
Esr2
+/−
→
Esr2
+/−
control constructs; both of which were more severe than the clinical signs observed in
Esr2
+/−
→ wild-type and wild-type → wild-type mice. These results indicate that the heterotic effect at
Esr2
is a function of the nonhematopoietic compartment.
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Details
- Title
- Estrogen Receptor-1 (Esr1) and -2 (Esr2) Regulate the Severity of Clinical Experimental Allergic Encephalomyelitis in Male Mice
- Creators
- Magdalena Polanczyk - From the Department of NeurologySrikanth Yellayi - From the Department of NeurologyAlex Zamora - From the Department of NeurologySandhya Subramanian - From the Department of NeurologyMicah Tovey - From the Department of NeurologyArthur A Vandenbark - From the Department of NeurologyHalina Offner - From the Department of NeurologyJames F Zachary - From the Department of NeurologyParley D Fillmore - From the Department of NeurologyElizabeth P Blankenhorn - From the Department of NeurologyJan-Åke Gustafsson - From the Department of NeurologyCory Teuscher - From the Department of Neurology
- Publication Details
- The American journal of pathology, v 164(6), pp 1915-1924
- Publisher
- American Society for Investigative Pathology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000221601000006
- Scopus ID
- 2-s2.0-2442637923
- Other Identifier
- 991014878330304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pathology