Immune Netw.  2003 Sep;3(3):248-254. 10.4110/in.2003.3.3.248.

Expression of Co-stimulatory Molecules and STAT/SOCS Signaling Factors in the Splenocytes of Mice Tolerized against Arthritis by Oral Administration of Type II Collagen

• Lee KE
• Hwang SY
• Min SY
• Kim HY

• KMID: 1615317
• DOI: http://doi.org/10.4110/in.2003.3.3.248

Abstract

Oral administration of antigen has long been used in the induction of immune tolerance in various animal models of autoimmune diseases including rheumatoid arthritis (RA). Alleveation of arthritogenic symptoms has been reported from RA patients who received oral administration of type II collagen (CII) without side effects, however its rather inconsistent therapeutic efficacy and variation among patients calls for more detailed investigation on the mechanism of oral tolerance to be settled as regular treatment for RA. In an attempt to understand the immunogenic processes underpinning tolerance induction by orally administered CII, we analyzed changes in the expression of costimulatory molecules and STAT/SOCS signaling messengers in the mouse model of collagen induced arthritis (CIA). We found thatin the spleen of CIA mice, that has been undergone repeated oral feeding of CII prior to the induction of arthritis, showed increased promortion of CTLA4 expressing lymphocytes than in the spleen of PBS fed control. On the other hand, cells expressing CD28 or ICOS were decreased in the spleen of tolerized mice. Tolerance induction by oral CII administration also enhanced the expression of STAT6 in both RNA and protein level, while not affecting the expression of STAT3. The expression of SOCS3, which hasbeen known to transmit STAT-mediated signals from Th2 type cytokines, remained unchanged in the spleen of tolerized mice. Interestingly transcript of SOCS1, which has been associated with Th1 related pathways, was only visible in the spleen of tolerized but not of control mice, suggesting that as in the case of IL-6 signaling, it may exert a feed back inhibition toward the Th1 type stimulation.

Keyword

Oral tolerance; rheumatoid arthritis; type II collagen; co-stimulatory molecules; STAT; SOCS

MeSH Terms

Administration, Oral*
Animals
Arthritis*
Arthritis, Rheumatoid
Autoimmune Diseases
Collagen
Collagen Type II*
Cytokines
Hand
Humans
Immune Tolerance
Interleukin-6
Lymphocytes
Mice*
Models, Animal
RNA
Spleen
Collagen
Collagen Type II
Cytokines
Interleukin-6
RNA